<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03245450</url>
  </required_header>
  <id_info>
    <org_study_id>E7389-G000-213</org_study_id>
    <secondary_id>2016-003352-67</secondary_id>
    <nct_id>NCT03245450</nct_id>
  </id_info>
  <brief_title>Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan Hydrochloride in Children With Refractory or Recurrent Solid Tumors</brief_title>
  <official_title>A Phase 1/2 Single-arm Study Evaluating the Safety and Efficacy of Eribulin Mesilate in Combination With Irinotecan in Children With Refractory or Recurrent Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Phase 1 part of the study is conducted to determine the maximum tolerated dose (MTD) and&#xD;
      Recommended Phase 2 Dose (RP2D) of eribulin mesilate in combination with irinotecan&#xD;
      hydrochloride in pediatric participants with relapsed/refractory solid tumors (excluding&#xD;
      central nervous system [CNS] tumors).&#xD;
&#xD;
      The Phase 2 part of the study is conducted to assess the objective response rate (ORR) and&#xD;
      duration of response (DOR) of eribulin mesilate in combination with irinotecan hydrochloride&#xD;
      in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS),&#xD;
      non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) and ewing sarcoma (EWS).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 5, 2018</start_date>
  <completion_date type="Actual">May 17, 2021</completion_date>
  <primary_completion_date type="Actual">May 17, 2021</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride</measure>
    <time_frame>First dose of study drug up to Cycle 1 (Cycle length=21 days)</time_frame>
    <description>The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities [DLTs]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase 2: Objective Response Rate (ORR)</measure>
    <time_frame>From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 4 months</time_frame>
    <description>ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (&lt;) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From first dose of study drug up to approximately 2 years 4 months</time_frame>
    <description>A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Serious Adverse Event (SAE)</measure>
    <time_frame>Up to approximately 2 years and 4 months</time_frame>
    <description>SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
    <description>Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, Total Clearance (CL) of Eribulin and Irinotecan</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
    <description>CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
    <description>Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38</measure>
    <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
    <description>AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Progression Free Survival (PFS)</measure>
    <time_frame>From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months</time_frame>
    <description>PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase 2: Clinical Benefit Rate (CBR)</measure>
    <time_frame>From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months</time_frame>
    <description>CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than [&gt;] 11 weeks). CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Model Predicted Apparent Total Body Clearance (CL) of Eribulin</measure>
    <time_frame>Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)</time_frame>
    <description>Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type &quot;Number&quot; defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution Estimates From the Population PK Model for Eribulin</measure>
    <time_frame>Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)</time_frame>
    <description>Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type &quot;Number&quot; defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Refractory or Recurrent Solid Tumors</condition>
  <condition>Rhabdomyosarcoma</condition>
  <condition>Non-Rhabdomyosarcoma Soft Tissue Sarcoma</condition>
  <condition>Ewing Sarcoma</condition>
  <arm_group>
    <arm_group_label>Eribulin mesilate plus irinotecan hydrochloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Schedules A and B, eribulin mesilate at the dose of 1.4 milligrams per meters squared (mg/m^2) will be administered as an intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle. In Schedule A, irinotecan hydrochloride at the doses of 20 mg/m^2 or 40 mg/m^2 will be administered as an IV infusion on Days 1 to 5 of a 21-day cycle. In Schedule B, irinotecan hydrochloride at the doses of 100 mg/m^2 or 125 mg/m^2 will be administered as an IV infusion on Days 1 and 8 of a 21-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Eribulin mesilate</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Eribulin mesilate plus irinotecan hydrochloride</arm_group_label>
    <other_name>E7389</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan hydrochloride</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Eribulin mesilate plus irinotecan hydrochloride</arm_group_label>
    <other_name>(S)-4,11-diethyl-39 3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-4-yl-[1,4'-bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Participants must be&#xD;
&#xD;
          -  &gt;=12 months to less than or equal to (&lt;=) 25 years old at the time of consent [no more&#xD;
             than 25 percent (%) of participants between the ages of 18 and 25 years will be&#xD;
             enrolled in this study].&#xD;
&#xD;
          -  In Phase 1, &gt;6 months and &lt;12 months at the time of consent (Schedule A only)&#xD;
             participants will be enrolled one dose level behind the &gt;=12 months participant in&#xD;
             order to maximize safety for infant participants. In Phase 2, participants aged &gt;6&#xD;
             months and &lt;12 months at the time of consent will be enrolled to Schedule A with a&#xD;
             modified dose of eribulin with the irinotecan dose maintained in order to maximize&#xD;
             safety for infant participants.&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Phase 1: Participants must be diagnosed with histologically confirmed solid tumors&#xD;
             (excluding CNS tumors), which is relapsed or refractory, and for which there are no&#xD;
             currently available therapies.&#xD;
&#xD;
          -  Phase 2: Participants must be diagnosed with histologically confirmed RMS, NRSTS or&#xD;
             EWS which is relapsed or refractory having received at least 1 prior therapy,&#xD;
             including primary treatment.&#xD;
&#xD;
          -  Phase 1: Participants must have either measurable or evaluable disease as per RECIST&#xD;
             1.1.&#xD;
&#xD;
          -  Phase 2: Participants must have measurable disease as per RECIST 1.1.&#xD;
&#xD;
          -  Participant's current disease state must be one for which there is no known curative&#xD;
             therapy.&#xD;
&#xD;
          -  Participant's performance score must be &gt;=50% Karnofsky (for participants &gt;16 years of&#xD;
             age) or Lansky (for participants &lt;=16 years of age).Participants who are unable to&#xD;
             walk because of paralysis and/or previous surgeries, but who are in a wheelchair, will&#xD;
             be considered ambulatory for the purpose of assessing the performance score.&#xD;
&#xD;
          -  Participants must have fully recovered from the acute toxic effects of all prior&#xD;
             anticancer treatments prior to study drug administration:&#xD;
&#xD;
               -  Must not have received myelosuppressive chemotherapy within 21 days prior to&#xD;
                  study drug administration (42 days if prior nitrosourea).&#xD;
&#xD;
               -  Must not have received a long-acting growth factor (example, Neulasta) within 14&#xD;
                  days or a short-acting growth factor within 7 days.&#xD;
&#xD;
               -  Must not have received an antineoplastic targeted therapy within 14 days.&#xD;
&#xD;
               -  Must not have received immunotherapy, example, tumor vaccines, within 42 days.&#xD;
&#xD;
               -  Must not have received monoclonal antibodies within at least 3 half-lives of the&#xD;
                  antibody after its last dose.&#xD;
&#xD;
               -  Must not have received radiotherapy (XRT) within 14 days prior to study drug&#xD;
                  administration (small field) or 42 days for craniospinal XRT, or if &gt;=50%&#xD;
                  radiation of pelvis.&#xD;
&#xD;
               -  At least 84 days must have elapsed after stem cell infusion prior to study drug&#xD;
                  administration&#xD;
&#xD;
               -  No evidence of active graft-versus-host disease (GVHD) and at least 100 days must&#xD;
                  have elapsed after allogeneic bone marrow transplant or stem cell infusion prior&#xD;
                  to study drug administration&#xD;
&#xD;
          -  Participants must have adequate bone marrow function, defined as:&#xD;
&#xD;
               -  Peripheral absolute neutrophil count (ANC) &gt;=1.0*10^9/liter (L).&#xD;
&#xD;
               -  Platelet count &gt;=100*10^9/L (not receiving platelet transfusions within a 7-day&#xD;
                  period prior to study drug administration).&#xD;
&#xD;
               -  Hemoglobin (Hb) at least 8.0 grams per deciliter (g/dL) at baseline (blood&#xD;
                  transfusions are allowed during the screening period to correct Hb values &lt;8.0&#xD;
                  g/dL).&#xD;
&#xD;
          -  Participants must have adequate renal function, defined as:&#xD;
&#xD;
               -  A serum creatinine based on age/gender, derived from the Schwartz formula for&#xD;
                  estimating glomerular filtration rate (GFR), per protocol-specified criteria.&#xD;
&#xD;
               -  Serum creatinine clearance or GFR &gt;=50 milliliters/minute/1.73 m^2, based on a 12&#xD;
                  or 24 hours (h) urine creatinine collection.&#xD;
&#xD;
          -  Participants must have adequate liver function, defined as:&#xD;
&#xD;
               -  Bilirubin (sum of conjugated + unconjugated) &lt;=1.5 times the upper limit of&#xD;
                  normal (ULN) for age.&#xD;
&#xD;
               -  Alkaline phosphatase, alanine aminotransferase (ALT) and aspartate&#xD;
                  aminotransferase (AST) &lt;=3*ULN (in the case of liver metastases &lt;=5*ULN), unless&#xD;
                  there are bone metastases, in which case liver-specific alkaline phosphatase must&#xD;
                  be separated from the total and used to assess the liver function instead of the&#xD;
                  total alkaline phosphatase.&#xD;
&#xD;
               -  Serum albumin &gt;=2 g/dL.&#xD;
&#xD;
          -  All participants and/or their parents or guardians must sign a written informed&#xD;
             consent.&#xD;
&#xD;
          -  Participants must be willing to comply with all aspects of the protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Females who are breastfeeding or pregnant at Screening or Baseline. A separate&#xD;
             baseline assessment is required if a negative screening pregnancy test was obtained&#xD;
             more than 72 h before the first dose of study drug.&#xD;
&#xD;
          -  Females of childbearing potential who:&#xD;
&#xD;
               -  Do not agree to use a highly effective method of contraception for the entire&#xD;
                  study period and for 6 months after study drug discontinuation, that is:&#xD;
&#xD;
               -  Total abstinence (if it is their preferred and usual lifestyle)&#xD;
&#xD;
               -  An intrauterine device (IUD) or intrauterine system (IUS)&#xD;
&#xD;
               -  A contraceptive implant&#xD;
&#xD;
               -  An oral contraceptive OR&#xD;
&#xD;
               -  Do not have a vasectomized partner with confirmed azoospermia.&#xD;
&#xD;
          -  Males who have not had a successful vasectomy (confirmed azoospermia) or they and&#xD;
             their female partners do not meet the criteria above (that is, not of childbearing&#xD;
             potential or practicing highly effective contraception throughout the study period or&#xD;
             for 3 months after study drug discontinuation). No sperm donation is allowed during&#xD;
             the study period or for 3 months after study drug discontinuation.&#xD;
&#xD;
          -  Concomitant Medications:&#xD;
&#xD;
               -  Participants receiving corticosteroids who have not been on a stable dose for at&#xD;
                  least 7 days prior to study drug administration.&#xD;
&#xD;
               -  Participants who are currently receiving other anticancer agents.&#xD;
&#xD;
               -  Participants who are receiving cyclosporine, tacrolimus or other agents to&#xD;
                  prevent GVHD post bone marrow transplant.&#xD;
&#xD;
               -  Participants who are receiving strong cytochrome P450 3A4 (CYP3A4) inhibitors and&#xD;
                  inducers including traditional herbal medicinal products (example, St. John's&#xD;
                  Wort).&#xD;
&#xD;
          -  Phase 1: Received prior therapy with eribulin mesilate within 6 months prior to study&#xD;
             drug administration.&#xD;
&#xD;
          -  Phase 2: Received prior therapies with eribulin mesilate or irinotecan hydrochloride&#xD;
             (for prior irinotecan hydrochloride, participants can be included if there was no&#xD;
             tumor progression during irinotecan therapy).&#xD;
&#xD;
          -  Any other malignancy that required treatment (except non-melanoma skin cancer, or&#xD;
             histologically confirmed complete excision of carcinoma in situ), within 2 years prior&#xD;
             to study drug administration.&#xD;
&#xD;
          -  Has hypersensitivity to either study drug or any of the excipients.&#xD;
&#xD;
          -  Has a known prior history of viral hepatitis (B or C) as demonstrated by positive&#xD;
             serology (presence of antigens) or have an uncontrolled infection requiring treatment&#xD;
&#xD;
          -  Has &gt;Grade 1 peripheral sensory neuropathy or &gt;Grade 1 peripheral motor neuropathy&#xD;
             graded according to the Modified (&quot;Balis&quot;) Pediatric Scale of Peripheral Neuropathies.&#xD;
&#xD;
          -  Has cardiac pathology, defined as:&#xD;
&#xD;
               -  Participants with known congestive heart failure, symptomatic or Left ventricular&#xD;
                  (LV) ejection fraction &lt;50% or shortening fraction &lt;27% and participants with&#xD;
                  congenital long QT syndrome, bradyarrhythmias, or QT interval (QTc)&gt;480&#xD;
                  milliseconds on at least 2 separate electrocardiograms (ECGs).&#xD;
&#xD;
          -  Has CNS disease: Participants with brain or subdural metastases are not eligible&#xD;
             unless the metastases are asymptomatic and do not require treatment or have been&#xD;
             adequately treated by local therapy and have discontinued the use of corticosteroids&#xD;
             for this indication for at least 28 days prior to study drug administration.&#xD;
             Participants must be clinically stable. It is not the intention of this protocol to&#xD;
             treat participants with active brain metastases.&#xD;
&#xD;
        Note: Screening CNS imaging for participants with a known history of CNS disease is&#xD;
        required.&#xD;
&#xD;
          -  Have had or are planning to have the following invasive procedures:&#xD;
&#xD;
               -  Major surgical procedure or significant traumatic injury within 28 days prior to&#xD;
                  study drug administration.&#xD;
&#xD;
               -  Laparoscopic procedure or open biopsy within 7 days prior to study drug&#xD;
                  administration&#xD;
&#xD;
               -  Central line placement or subcutaneous port placement is not considered major&#xD;
                  surgery.&#xD;
&#xD;
               -  Core biopsy, including bone marrow biopsy within 2 days prior to study drug&#xD;
                  administration.&#xD;
&#xD;
               -  Fine needle aspirate within 3 days prior to study drug administration.&#xD;
&#xD;
          -  Participants with known human immunodeficiency virus (HIV); due to lack of available&#xD;
             safety data for eribulin therapy in HIV infected participants.&#xD;
&#xD;
          -  Has any serious concomitant illness that in the opinion of the investigator(s) could&#xD;
             affect the participant's safety or interfere with the study assessments (including&#xD;
             active or severe chronic inflammatory bowel disease or bowel obstruction).&#xD;
&#xD;
          -  Has received a live-virus vaccination within 30 days of planned start of study&#xD;
             therapy. Seasonal flu vaccines that do not contain live virus are permitted.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hopitaux de La Timone</name>
      <address>
        <city>Marseille</city>
        <state>Bouches-du-Rhône</state>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <state>Nord</state>
        <zip>59020</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Léon Berard</name>
      <address>
        <city>Lyon</city>
        <state>Rhône</state>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 4</name>
      <address>
        <city>Freiburg</city>
        <state>Baden-Württemberg</state>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 2</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 5</name>
      <address>
        <city>Gottingen</city>
        <state>Niedersachsen</state>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 1</name>
      <address>
        <city>Aachen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 3</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 6</name>
      <address>
        <city>Essen</city>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aghia Sophia' Children's General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AHEPA University General Hospital of Thessaloniki</name>
      <address>
        <city>Thessaloníki</city>
        <zip>546 36</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Pediatrico Bambino Gesù</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario A Gemelli</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto G Gaslini Ospedale Pediatrico IRCCS</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16147</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Infantile Regina Margherita</name>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera A Meyer</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <zip>50139</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Di Padova</name>
      <address>
        <city>Padova</city>
        <state>Veneto</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Dei Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu</name>
      <address>
        <city>Wrocław</city>
        <state>Dolnoslaskie</state>
        <zip>50-556</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instytut Pomnik Centrum Zdrowia Dziecka</name>
      <address>
        <city>Warszawa</city>
        <state>Mazowieckie</state>
        <zip>04-730</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron - PPDS</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluña</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan de Deu</name>
      <address>
        <city>Esplugues De Llobregat</city>
        <state>Cataluña</state>
        <zip>08950</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infantil Universitario Niño Jesus</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kinderspital Zürich - Eleonorenstiftung</name>
      <address>
        <city>Zürich</city>
        <zip>CH-8032</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <state>Hampshire</state>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alder Hey Childrens Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>Merseyside</state>
        <zip>L12 2AP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Radcliffe Hospital</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 9DU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital - Surrey</name>
      <address>
        <city>Sutton</city>
        <state>Surrey</state>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Children's Hospital</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Leeds Teaching Hospitals Charitable Foundation - Leeds Childrens Hospital (LCH)</name>
      <address>
        <city>Leeds</city>
        <state>Yorkshire</state>
        <zip>LS1 3EX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London</name>
      <address>
        <city>London</city>
        <zip>NW1 2BU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Manchester Childrens Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christie NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Victoria Infirmary</name>
      <address>
        <city>Newcastle</city>
        <zip>NE1 4LP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Italy</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <results_first_submitted>May 16, 2022</results_first_submitted>
  <results_first_submitted_qc>June 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">June 28, 2022</results_first_posted>
  <last_update_submitted>June 20, 2022</last_update_submitted>
  <last_update_submitted_qc>June 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>eribulin mesilate</keyword>
  <keyword>irinotecan</keyword>
  <keyword>combination therapy</keyword>
  <keyword>children</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irinotecan</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 29, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03245450/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03245450/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 22 investigative sites in France, Germany, Greece, Italy, Poland, Spain and United Kingdom from 05 March 2018 to 17 May 2021.</recruitment_details>
      <pre_assignment_details>A total of 46 participants were screened, out of which 13 participants were treated in the Phase 1 and 27 participants were treated in Phase 2 (9 participants each in the relapsed/refractory rhabdomyosarcoma [RMS], non-rhabdomyosarcoma soft tissue sarcoma [NRSTS], and Ewing sarcoma [EWS] cohorts).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 (milligram per square meter) intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="P2">
          <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="P3">
          <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="P4">
          <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="P5">
          <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="P6">
          <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="P7">
          <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="9"/>
                <participants group_id="P7" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="9"/>
                <participants group_id="P7" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Radiological disease progression</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="7"/>
                <participants group_id="P6" count="6"/>
                <participants group_id="P7" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Clinical disease progression</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="1"/>
                <participants group_id="P7" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B2">
          <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B3">
          <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B4">
          <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B5">
          <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B6">
          <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B7">
          <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="B8">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="3"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="9"/>
            <count group_id="B6" value="9"/>
            <count group_id="B7" value="9"/>
            <count group_id="B8" value="40"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Per the planned analysis, baseline data for participants in Phase 1 and Phase 2 were not combined, therefore Mean and Standard Deviation are presented separately for Phase 1 and Phase 2 participants.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Phase 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="0"/>
                    <count group_id="B6" value="0"/>
                    <count group_id="B7" value="0"/>
                    <count group_id="B8" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.94" spread="6.583"/>
                    <measurement group_id="B2" value="7.33" spread="2.540"/>
                    <measurement group_id="B3" value="13.97" spread="4.231"/>
                    <measurement group_id="B4" value="8.06" spread="4.997"/>
                    <measurement group_id="B8" value="9.87" spread="4.842"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Phase 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="9"/>
                    <count group_id="B6" value="9"/>
                    <count group_id="B7" value="9"/>
                    <count group_id="B8" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B5" value="11.05" spread="3.845"/>
                    <measurement group_id="B6" value="12.71" spread="4.348"/>
                    <measurement group_id="B7" value="11.59" spread="3.753"/>
                    <measurement group_id="B8" value="11.78" spread="3.899"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="9"/>
                    <count group_id="B6" value="9"/>
                    <count group_id="B7" value="9"/>
                    <count group_id="B8" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Children (2-11 years)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="4"/>
                    <measurement group_id="B8" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Adolescents (12-17 years)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="5"/>
                    <measurement group_id="B8" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="9"/>
                    <count group_id="B6" value="9"/>
                    <count group_id="B7" value="9"/>
                    <count group_id="B8" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="5"/>
                    <measurement group_id="B8" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="7"/>
                    <measurement group_id="B7" value="4"/>
                    <measurement group_id="B8" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="9"/>
                    <count group_id="B6" value="9"/>
                    <count group_id="B7" value="9"/>
                    <count group_id="B8" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="9"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="9"/>
                    <measurement group_id="B8" value="38"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="3"/>
                    <count group_id="B2" value="4"/>
                    <count group_id="B3" value="3"/>
                    <count group_id="B4" value="3"/>
                    <count group_id="B5" value="9"/>
                    <count group_id="B6" value="9"/>
                    <count group_id="B7" value="9"/>
                    <count group_id="B8" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="5"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="8"/>
                    <measurement group_id="B8" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                    <measurement group_id="B8" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                    <measurement group_id="B8" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride</title>
        <description>The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities [DLTs]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.</description>
        <time_frame>First dose of study drug up to Cycle 1 (Cycle length=21 days)</time_frame>
        <population>The Dose Evaluable Set (DES) for Phase 1 included all the participants who completed Cycle 1 treatment and were evaluated for DLTs and those who discontinued treatment during Cycle 1 due to DLTs.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: All Participants</title>
            <description>All participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2 or 40 mg/m^2 intravenous infusion on Days 1 to 5 (schedule A) and irinotecan hydrochloride 100 mg/m^2 or 125 mg/m^2 intravenous infusion on Days 1 and 8 (schedule B) in 21-day treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride</title>
          <description>The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities [DLTs]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.</description>
          <population>The Dose Evaluable Set (DES) for Phase 1 included all the participants who completed Cycle 1 treatment and were evaluated for DLTs and those who discontinued treatment during Cycle 1 due to DLTs.</population>
          <units>mg/m^2</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin Mesilate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan Hydrochloride</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase 2: Objective Response Rate (ORR)</title>
        <description>ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (&lt;) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 4 months</time_frame>
        <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Objective Response Rate (ORR)</title>
          <description>ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (&lt;) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" spread="0.6" lower_limit="0.6" upper_limit="42.9"/>
                    <measurement group_id="O2" value="11.1" spread="0.6" lower_limit="0.6" upper_limit="42.9"/>
                    <measurement group_id="O3" value="11.1" spread="0.6" lower_limit="0.6" upper_limit="42.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.</description>
        <time_frame>From first dose of study drug up to approximately 2 years 4 months</time_frame>
        <population>Safety analysis set included all participants who received at least 1 dose of either study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O6">
            <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O7">
            <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.</description>
          <population>Safety analysis set included all participants who received at least 1 dose of either study drug.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="9"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="9"/>
                    <measurement group_id="O6" value="9"/>
                    <measurement group_id="O7" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Serious Adverse Event (SAE)</title>
        <description>SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.</description>
        <time_frame>Up to approximately 2 years and 4 months</time_frame>
        <population>Safety analysis set included all participants who received at least 1 dose of either study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O6">
            <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O7">
            <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious Adverse Event (SAE)</title>
          <description>SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.</description>
          <population>Safety analysis set included all participants who received at least 1 dose of either study drug.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="9"/>
                <count group_id="O6" value="9"/>
                <count group_id="O7" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="5"/>
                    <measurement group_id="O6" value="4"/>
                    <measurement group_id="O7" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.</population>
          <units>nanogram/milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="369.3" spread="58.0" lower_limit="58.0"/>
                    <measurement group_id="O2" value="179.4" spread="136.1" lower_limit="136.1"/>
                    <measurement group_id="O3" value="348.7" spread="25.0" lower_limit="25.0"/>
                    <measurement group_id="O4" value="323.3" spread="20.6" lower_limit="20.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="538.8" spread="165.9" lower_limit="165.9"/>
                    <measurement group_id="O2" value="399.5" spread="19.1" lower_limit="19.1"/>
                    <measurement group_id="O3" value="1168.1" spread="39.8" lower_limit="39.8"/>
                    <measurement group_id="O4" value="1555.4" spread="39.5" lower_limit="39.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Active Metabolite SN-38</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.518" spread="9.4" lower_limit="9.4"/>
                    <measurement group_id="O2" value="17.170" spread="39.7" lower_limit="39.7"/>
                    <measurement group_id="O3" value="25.409" spread="51.6" lower_limit="51.6"/>
                    <measurement group_id="O4" value="18.614" spread="74.3" lower_limit="74.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.080" spread="0.03" lower_limit="0.03" upper_limit="0.22"/>
                    <measurement group_id="O2" value="0.135" spread="0.03" lower_limit="0.03" upper_limit="1"/>
                    <measurement group_id="O3" value="0.080" spread="0" lower_limit="0" upper_limit="0.12"/>
                    <measurement group_id="O4" value="0.050" spread="0.01" lower_limit="0.01" upper_limit="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.250" spread="0.07" lower_limit="0.07" upper_limit="0.42"/>
                    <measurement group_id="O2" value="0.305" spread="0" lower_limit="0" upper_limit="24"/>
                    <measurement group_id="O3" value="0.300" spread="0.03" lower_limit="0.03" upper_limit="0.33"/>
                    <measurement group_id="O4" value="0.170" spread="0.13" lower_limit="0.13" upper_limit="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Active Metabolite SN-38</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.420" spread="0.25" lower_limit="0.25" upper_limit="1.03"/>
                    <measurement group_id="O2" value="0.305" spread="0" lower_limit="0" upper_limit="24"/>
                    <measurement group_id="O3" value="0.330" spread="0.3" lower_limit="0.3" upper_limit="0.53"/>
                    <measurement group_id="O4" value="0.250" spread="0.13" lower_limit="0.13" upper_limit="0.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
        <description>Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
          <description>Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.50" lower_limit="26.5" upper_limit="27.7"/>
                    <measurement group_id="O2" value="34.70" lower_limit="32.9" upper_limit="40.4"/>
                    <measurement group_id="O3" value="30.00" lower_limit="23.4" upper_limit="43.3"/>
                    <measurement group_id="O4" value="25.30" lower_limit="22.1" upper_limit="28.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="5.140" lower_limit="5.1" upper_limit="9.61"/>
                    <measurement group_id="O4" value="4.430" lower_limit="3.95" upper_limit="5.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolite SN-38</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="12.000" lower_limit="9.9" upper_limit="13.9"/>
                    <measurement group_id="O4" value="10.390" lower_limit="9.68" upper_limit="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, Total Clearance (CL) of Eribulin and Irinotecan</title>
        <description>CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, Total Clearance (CL) of Eribulin and Irinotecan</title>
          <description>CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
          <units>liter per hour (L/h)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1781" spread="43.9"/>
                    <measurement group_id="O2" value="2.4581" spread="8.0"/>
                    <measurement group_id="O3" value="2.9060" spread="32.8"/>
                    <measurement group_id="O4" value="1.7521" spread="136.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="27.27" spread="23.2"/>
                    <measurement group_id="O4" value="30.30" spread="60.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan</title>
        <description>Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan</title>
          <description>Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
          <units>liter</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="124.70" spread="41.5"/>
                    <measurement group_id="O2" value="126.96" spread="18.1"/>
                    <measurement group_id="O3" value="130.78" spread="35.9"/>
                    <measurement group_id="O4" value="63.35" spread="101.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="248.5" spread="16.1"/>
                    <measurement group_id="O4" value="195.1" spread="69.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration.</population>
          <units>hour*nanogram per milliliter (h*ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="422.5" spread="40.0" lower_limit="40.0"/>
                    <measurement group_id="O2" value="403.7" spread="32.1" lower_limit="32.1"/>
                    <measurement group_id="O3" value="616.9" spread="66.1" lower_limit="66.1"/>
                    <measurement group_id="O4" value="603.5" spread="87.3" lower_limit="87.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1812.6" spread="13.5" lower_limit="13.5"/>
                    <measurement group_id="O2" value="3686.1" spread="36.4" lower_limit="36.4"/>
                    <measurement group_id="O3" value="4693.9" spread="66.1" lower_limit="66.1"/>
                    <measurement group_id="O4" value="3633.7" spread="38.9" lower_limit="38.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolite SN-38</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.00" spread="19.7" lower_limit="19.7"/>
                    <measurement group_id="O2" value="145.04" spread="11.6" lower_limit="11.6"/>
                    <measurement group_id="O3" value="138.22" spread="42.2" lower_limit="42.2"/>
                    <measurement group_id="O4" value="65.47" spread="153.2" lower_limit="153.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
        <description>AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
        <time_frame>For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
            <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38</title>
          <description>AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.</description>
          <population>PK analysis set included participants who had documented dosing history and at least one post-dosing quantifiable drug concentration. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable for each category.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Eribulin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="438.1" spread="39.0"/>
                    <measurement group_id="O2" value="506.0" spread="16.6"/>
                    <measurement group_id="O3" value="666.9" spread="69.0"/>
                    <measurement group_id="O4" value="576.9" spread="133.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Irinotecan</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="5036.1" spread="70.9"/>
                    <measurement group_id="O4" value="3698.5" spread="39.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolite SN-38</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="0"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="169.0" spread="51.4"/>
                    <measurement group_id="O4" value="149.4" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Progression Free Survival (PFS)</title>
        <description>PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.</description>
        <time_frame>From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months</time_frame>
        <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Progression Free Survival (PFS)</title>
          <description>PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.</description>
          <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.69" spread="1.28" lower_limit="1.28" upper_limit="8.87"/>
                    <measurement group_id="O2" value="1.35" spread="1.15" lower_limit="1.15" upper_limit="2.79"/>
                    <measurement group_id="O3" value="6.70" spread="1.38" lower_limit="1.38" upper_limit="8.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase 2: Clinical Benefit Rate (CBR)</title>
        <description>CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than [&gt;] 11 weeks). CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months</time_frame>
        <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
            <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 2: Clinical Benefit Rate (CBR)</title>
          <description>CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than [&gt;] 11 weeks). CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis &lt;10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Full analysis set included all participants who received at least 1 dose of either study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.6" spread="25.1" lower_limit="25.1" upper_limit="83.1"/>
                    <measurement group_id="O2" value="33.3" spread="9.8" lower_limit="9.8" upper_limit="65.5"/>
                    <measurement group_id="O3" value="55.6" spread="25.1" lower_limit="25.1" upper_limit="83.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Model Predicted Apparent Total Body Clearance (CL) of Eribulin</title>
        <description>Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type &quot;Number&quot; defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.</description>
        <time_frame>Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885).&quot;Overall number of participants analyzed&quot; signifies participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Eribulin Mesilate - All Participants</title>
            <description>All participants who received eribulin mesilate intravenous infusion over the dose range 0.25 to 4.0 mg/m^2 in current study (E7389-G000-213) and studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885).</description>
          </group>
        </group_list>
        <measure>
          <title>Model Predicted Apparent Total Body Clearance (CL) of Eribulin</title>
          <description>Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type &quot;Number&quot; defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.</description>
          <population>PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885).&quot;Overall number of participants analyzed&quot; signifies participants who were evaluable for this outcome measure.</population>
          <units>L/hr</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="561"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.89" lower_limit="2.75" upper_limit="3.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution Estimates From the Population PK Model for Eribulin</title>
        <description>Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type &quot;Number&quot; defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.</description>
        <time_frame>Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)</time_frame>
        <population>PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885).&quot;Overall number of participants analyzed&quot; signifies participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Eribulin Mesilate - All Participants</title>
            <description>All participants who received eribulin mesilate intravenous infusion over the dose range 0.25 to 4.0 mg/m^2 in current study (E7389-G000-213) and in studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885).</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution Estimates From the Population PK Model for Eribulin</title>
          <description>Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type &quot;Number&quot; defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.</description>
          <population>PK analysis set included all participants who had documented dosing history had at least one postdosing quantifiable drug concentration. Analysis population for this outcome measure included participants from current study E7389-G000-213 and from studies (NCT00069264,NCT00069277,NCT00326950,NCT00706095,NCT01000376,NCT01106248,NCT02171260, NCT00413192,NCT01458249,NCT03441360,NCT01327885).&quot;Overall number of participants analyzed&quot; signifies participants who were evaluable for this outcome measure.</population>
          <units>liter</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="561"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>V1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.08" lower_limit="3.87" upper_limit="4.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>V2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.03" lower_limit="1.79" upper_limit="2.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>V3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106" lower_limit="101" upper_limit="111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug up to approximately 2 year 4 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 20 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 20 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="E2">
          <title>Phase 1: Schedule A, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="E3">
          <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 100 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 100 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="E4">
          <title>Phase 1: Schedule B, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 125 mg/m^2</title>
          <description>Participants received eribulin mesilate 1.4 mg/m^2 and irinotecan hydrochloride 125 mg/m^2 intravenous infusion on Days 1 and 8 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="E5">
          <title>Phase 2: RMS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with RMS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of intolerable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="E6">
          <title>Phase 2: NRSTS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with NRSTS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
        </group>
        <group group_id="E7">
          <title>Phase 2: EWS Cohort, Eribulin Mesilate 1.4 mg/m^2 + Irinotecan 40 mg/m^2</title>
          <description>Participants with EWS received eribulin mesilate 1.4 mg/m^2, intravenous infusion on Days 1 and 8 and Irinotecan hydrochloride 40 mg/m^2, intravenous infusion on Days 1 to 5 in every 21 days treatment cycle until disease progression, development of unacceptable toxicity or withdrawal of consent.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 24.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E6" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E7" subjects_affected="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="14" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="6" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="9" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E6" events="8" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E7" events="29" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="14" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="15" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="12" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="32" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="39" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" events="8" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="18" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="12" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="15" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E6" events="10" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="52" subjects_affected="4" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="17" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="9" subjects_affected="7" subjects_at_risk="9"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="12" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="24" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E6" events="11" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E7" events="9" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E6" events="8" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E3" events="10" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E4" events="3" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="8" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Anal fissure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Anal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Aphthous ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Gingival pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Haematemesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia oral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="5" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Tongue ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="8" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Catheter site pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="5" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E7" events="4" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Ear infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Herpes simplex</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Urostomy complication</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Mouth injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="10" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="9" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="5" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="8" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="5" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="8" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="7" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" events="21" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E6" events="22" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E7" events="46" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="7" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="20" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="6" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood calcium decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood phosphorus decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood sodium decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Haematocrit decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="7" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Metamyelocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Myelocyte count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Red blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="5" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="5" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="7" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="10" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Refeeding syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="4" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="3" subjects_affected="3" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="5" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="5" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E7" events="4" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pain in jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="6" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Peripheral sensorimotor neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="8" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Negative thoughts</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Tearfulness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Urinary tract pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Respiratory distress</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Allergic cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Laryngeal inflammation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Skin oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Leukonychia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Papule</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E7" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Eisai Medical Information</name_or_title>
      <organization>Eisai Inc.</organization>
      <phone>1-888-274-2378</phone>
      <email>esi_oncmedinfo@eisai.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03245450
org study id: E7389-G000-213
secondary id: 2016-003352-67
nct id: NCT03245450
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The Phase 1 part of the study is conducted to determine the maximum tolerated dose (MTD) and
      Recommended Phase 2 Dose (RP2D) of eribulin mesilate in combination with irinotecan
      hydrochloride in pediatric participants with relapsed/refractory solid tumors (excluding
      central nervous system [CNS] tumors).

      The Phase 2 part of the study is conducted to assess the objective response rate (ORR) and
      duration of response (DOR) of eribulin mesilate in combination with irinotecan hydrochloride
      in pediatric participants with relapsed/refractory rhabdomyosarcoma (RMS),
      non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) and ewing sarcoma (EWS).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Recommended Phase 2 Dose (RP2D) of Eribulin Mesilate in Combination With Irinotecan Hydrochloride
time frame: First dose of study drug up to Cycle 1 (Cycle length=21 days)
description: The RP2D was evaluated based on a review of the outcomes of safety (including dose limiting toxicities [DLTs]), tumor assessments, and pharmacokinetic (PK) in Phase 1 by investigators and the study team.
measure: Phase 2: Objective Response Rate (ORR)
time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 4 months
description: ORR was defined as the percentage of participants achieving best overall response (BOR) of confirmed partial response (PR) or complete response (CR) determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis less than (<) 10 millimeter (mm). PR was at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: From first dose of study drug up to approximately 2 years 4 months
description: A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment, or reemerged during treatment, having been present at pre-treatment (baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
measure: Number of Participants With Serious Adverse Event (SAE)
time frame: Up to approximately 2 years and 4 months
description: SAE was defined as any untoward medical occurrence at any dose if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.
measure: Phase 1, Cmax: Maximum Observed Plasma Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
measure: Phase 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Eribulin, Irinotecan and Its Active Metabolite SN-38
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
measure: Phase 1, T1/2: Half-life of Eribulin, Irinotecan and Its Active Metabolite SN-38
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
description: Half-life for irinotecan and metabolite SN-38 could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm as the slope of the terminal phase of the concentration-time profiles could not be determined.
measure: Phase 1, Total Clearance (CL) of Eribulin and Irinotecan
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
description: CL for irinotecan could not be estimated for phase 1:schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
measure: Phase 1, Volume of Distribution (Vz) of Eribulin and Irinotecan
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
description: Vz for irinotecan could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
measure: Phase 1, AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Eribulin, Irinotecan and Its Active Metabolite SN-38
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
measure: Phase 1, AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Eribulin, Irinotecan and Its Active Metabolite SN-38
time frame: For eribulin, Cycle 1 Day 1: 0-120 hours post-eribulin infusion; For irinotecan and its metabolite, Cycle 1 Day 1: 0-24 hours post-irinotecan infusion (cycle length=21 days)
description: AUC(0-inf) for irinotecan and metabolite SN-38 could not be estimated for phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 20 mg/m^2 and phase 1: schedule A, eribulin mesilate 1.4 mg/m^2 + irinotecan 40 mg/m^2 arm because it was not possible to calculate half-life as the slope of the terminal phase of the concentration-time profiles could not be determined.
measure: Phase 2: Progression Free Survival (PFS)
time frame: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months
description: PFS was defined as the time from date of first dose to the date of disease progression (PD). PFS was assessed based on the investigators' assessments utilizing RECIST 1.1. PD was defined as at least 20% increase or 5 mm increase in the sum of diameters of target lesions recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
measure: Phase 2: Clinical Benefit Rate (CBR)
time frame: From the date of first dose to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 2 years 4 months
description: CBR was defined as the percentage of participants with BOR of CR, PR, or durable stable disease (SD) based on RECIST 1.1 (durable SD was defined as SD with duration of greater than [>] 11 weeks). CR was defined as disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters.
measure: Model Predicted Apparent Total Body Clearance (CL) of Eribulin
time frame: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)
description: Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. The data presented are the CL parameter estimates, with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.
measure: Volume of Distribution Estimates From the Population PK Model for Eribulin
time frame: Cycle 1 Day 1: 0.5-120 hours after eribulin infusion; Cycle 1 Day 8: pre-dose and at the end of the eribulin infusion (cycle length=21 days)
description: Per the planned PK analysis, PK samples were collected and analyzed using a population PK approach to estimate PK parameters. Eribulin plasma concentration data from this study were pooled from studies (NCT00069264, NCT00069277, NCT00326950, NCT00706095, NCT01000376, NCT01106248, NCT02171260, NCT00413192, NCT01458249, NCT03441360 and NCT01327885), and a population PK model was applied to the pooled dataset. Data presented are the volume of distribution of the central compartment (V1), volume of distribution of the first peripheral compartment (V2), and volume of distribution of the second peripheral compartment (V3) parameter estimates with Measure Type "Number" defining the eribulin PK model. They are population PK model predictions and have been estimated using non-linear mixed effects model.
arm group label: Eribulin mesilate plus irinotecan hydrochloride
arm group type: Experimental
description: In Schedules A and B, eribulin mesilate at the dose of 1.4 milligrams per meters squared (mg/m^2) will be administered as an intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle. In Schedule A, irinotecan hydrochloride at the doses of 20 mg/m^2 or 40 mg/m^2 will be administered as an IV infusion on Days 1 to 5 of a 21-day cycle. In Schedule B, irinotecan hydrochloride at the doses of 100 mg/m^2 or 125 mg/m^2 will be administered as an IV infusion on Days 1 and 8 of a 21-day cycle.
intervention type: Drug
intervention name: Eribulin mesilate
description: IV infusion
arm group label: Eribulin mesilate plus irinotecan hydrochloride
other name: E7389
intervention type: Drug
intervention name: Irinotecan hydrochloride
description: IV infusion
arm group label: Eribulin mesilate plus irinotecan hydrochloride
other name: (S)-4,11-diethyl-39 3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-4-yl-[1,4'-bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate
criteria: 
gender: All
minimum age: 6 Months
maximum age: 25 Years
healthy volunteers: No
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country: France
country: Germany
country: Greece
country: Italy
country: Poland
country: Spain
country: Switzerland
country: United Kingdom
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Rhabdomyosarcoma
mesh term: Sarcoma, Ewing
mesh term: Recurrence
mesh term: Irinotecan
provided document: 
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certain agreements: 
point of contact: 