<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/NCT03041701</url>
  </required_header>
  <id_info>
    <org_study_id>170049</org_study_id>
    <secondary_id>17-C-0049</secondary_id>
    <nct_id>NCT03041701</nct_id>
  </id_info>
  <brief_title>Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in People With Embryonal and Alveolar Rhabdomyosarcoma</brief_title>
  <official_title>A Phase I/II Trial of the Insulin-Like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in Patients With Embryonal and Alveolar Rhabdomyosarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</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>
      Background:&#xD;
&#xD;
      Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Two types are&#xD;
      embryonal RMS (ERMS) and alveolar RMS (ARMS). Dasatinib may block over-expression of a&#xD;
      certain enzyme. Ganitumab may block a certain growth factor, which might suppress tumor&#xD;
      growth. This drug combination may help slow tumor growth in people with ERMS and ARMS.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To see if dasatinib combined with ganitumab is safe and shrinks or slows the growth of tumors&#xD;
      in people with ERMS and ARMS.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People any age who have ERMS or ARMS that did not respond to previous treatment and who can&#xD;
      swallow tablets&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
        -  Medical history&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Blood, urine, and heart tests&#xD;
&#xD;
        -  Scans/x-rays&#xD;
&#xD;
        -  Tissue sample: This can be from previous surgery or biopsy.&#xD;
&#xD;
        -  Optional biopsy: A small piece of the tumor is removed with a needle.&#xD;
&#xD;
      Participants will be asked to co-enroll in another protocol.&#xD;
&#xD;
      Participants will get a drug interaction handout and wallet card that show what foods and&#xD;
      medications to avoid.&#xD;
&#xD;
      Participants will be treated in cycles. The first cycle is 35 days, and the rest are 28 days.&#xD;
      Participants will take dasatinib by mouth daily. They will get ganitumab through an&#xD;
      intravenous (IV) every 2 weeks. They will have a physical exam every 1-2 weeks, and urine and&#xD;
      heart tests before most cycles.&#xD;
&#xD;
      Participants will continue treatment as long as they do not have severe side effects, or&#xD;
      their tumors do not get worse.&#xD;
&#xD;
      After ending treatment, participants will have a visit. This includes repeats of the&#xD;
      screening tests.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
        -  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. The annual&#xD;
           incidence in the United States is 4-7 cases per million children under 15 years, which&#xD;
           represents 250 new cases per year. Two major histologic subtypes exist: embryonal&#xD;
           rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS), the latter of which&#xD;
           carries a particularly poor prognosis.&#xD;
&#xD;
        -  Over-expression of both the type like growth factor 1 (1 IGF) receptor insulin-like&#xD;
           growth factor type 1 receptor (IGF-1R) and its ligands has been observed in multiple&#xD;
           malignancies, including pediatric sarcomas, and abnormal activation of this pathway&#xD;
           contributes to sarcoma development and progression. Downstream signaling cascades of&#xD;
           IGF-1R further regulate tumor cell proliferation, survival, and metastasis through the&#xD;
           mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK)&#xD;
           and phosphatidylinositol 3-kinases (PI3Ks)/mammalian target of rapamycin (mTOR)&#xD;
           pathways. In the majority of RMS, IGF-1R is highly expressed.&#xD;
&#xD;
        -  Monoclonal antibodies targeting IGF-1R interfere with ligand binding and decrease the&#xD;
           expression of the receptor on cell surfaces by internalization and degradation of the&#xD;
           receptor. A number of these have been tested in the clinical setting. Results from a&#xD;
           phase II trial using monotherapy with monoclonal antibodies against IGF-1R resulted in&#xD;
           clinically meaningful responses in about 10-15% of patients with RMS. However, the vast&#xD;
           majority of these responses were short-lived with a rapid onset of resistance.&#xD;
&#xD;
        -  YES is a member of the SRC family tyrosine kinases (SFKs), non-receptor tyrosine kinases&#xD;
           that function in a number of signaling pathways necessary for cell growth,&#xD;
           differentiation and survival. Preclinical work suggests involvement of YES in a number&#xD;
           of solid tumor types, including colon carcinoma, oral squamous cell carcinoma, glioma,&#xD;
           pancreatic cancer, mesothelioma, and RMS.&#xD;
&#xD;
        -  Recently, the Helman lab published preclinical work showing that in both embryonal and&#xD;
           alveolar RMS models, blockade of IGF-1R results in YES activation and that YES&#xD;
           activation is associated with resistance to IGF-1R blockade. In addition, combination&#xD;
           blockade of IGF-1R and YES in vitro results in downregulation of phospho-AKT in some&#xD;
           cell lines. Treatment blocking both IGF-1R and YES results in enhanced growth inhibition&#xD;
           of multiple cell lines of both embryonal and alveolar RMS in vitro and in vivo.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. Phase I: To determine the safe dose of dasatinib when given with ganitumab in patients&#xD;
           with relapsed or refractory embryonal or alveolar RMS.&#xD;
&#xD;
        2. Phase II: To determine if the use of ganitumab plus dasatinib is able to be associated&#xD;
           with a modest fraction of patients who experience an objective clinical response&#xD;
           (complete response (CR) and partial response (PR) as defined by Response Evaluation&#xD;
           Criteria in Solid Tumors (RECIST) criteria. In addition, a second primary objective will&#xD;
           estimate the fraction that is without progression at 4 months.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  Patients must have a diagnosis of relapsed or refractory embryonal or alveolar RMS, be&#xD;
           able to swallow tablets, have archival tissue available.&#xD;
&#xD;
        -  Patients must have adequate performance status and adequate major organ function and&#xD;
           have recovered from acute toxicity of all prior therapies.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  This is an open label, multi-site, phase I/II study designed to determine if ganitumab&#xD;
           given in combination with dasatinib in children and adults with relapsed or refractory&#xD;
           embryonal or alveolar RMS for whom no curative options exist.&#xD;
&#xD;
        -  In the phase I portion, using a standard 3 + 3 design, limited dose escalations will be&#xD;
           performed to define the maximum tolerated dose (MTD) or the highest safe dose tested of&#xD;
           dasatinib when given in combination with ganitumab in this patient population.&#xD;
&#xD;
        -  In the phase II component, sixteen (16) evaluable patients, including up to 6 patients&#xD;
           from the phase I portion treated at the selected phase II dose, will be enrolled to rule&#xD;
           out a 5% fraction with a clinical response in favor of a 30% fraction with a clinical&#xD;
           response, using a one sided 0.10 significance level exact test for a binomial&#xD;
           proportion. In practice, the fraction of the 16 patients that have objective responses&#xD;
           will be determined and reported along with 80% and 95% confidence intervals. If there&#xD;
           are 3 objective responses in 16 evaluable patients, the lower one-sided exact 90%&#xD;
           confidence interval is 7.1%, thus ruling out 5%.&#xD;
&#xD;
        -  It is anticipated that approximately 10-15 patients per year may be accrued onto this&#xD;
           trial. Thus, 2 to 3 years is expected to completed accrual.&#xD;
&#xD;
        -  In all patients, mechanisms of response and resistance will be assessed by analyzing&#xD;
           archival tissue for expression of IGF-1R, insulin receptor, IGF-2 expression and&#xD;
           phospho-YES expression, and through genomic sequencing (on protocol 10-C-0086). Genomic&#xD;
           sequencing of tumor cells from tissue relative to non-tumor cells from whole blood will&#xD;
           be profiled to identify the genomic variances that may contribute to response or disease&#xD;
           progression and provide an understanding of molecular abnormalities. Ribonucleic acid&#xD;
           (RNA) sequencing will be conducted to provide expression data and give relevance to&#xD;
           deoxyribonucleic acid (DNA) mutations; Quantitative proteomics analysis will be&#xD;
           conducted on all patients to determine the exact amounts of specific proteins and/or to&#xD;
           confirm expression of genes that are correlative of response and disease progression.&#xD;
           Genomic and transcriptomic analysis will be conducted on patients who consent to&#xD;
           protocol 10-C-0086, Comprehensive Omics Analysis of Pediatric Solid Tumors and&#xD;
           Establishment of a Repository for Related Biological Studies. All genomic,&#xD;
           transcriptomic, and proteomic molecular analyses will be retrospective and exploratory.&#xD;
&#xD;
        -  In patients who agree to undergo biopsy of their tumor, provided the tissue is easily&#xD;
           accessible and can be biopsied safely with minimal morbidity, mechanisms of response and&#xD;
           resistance will be assessed by analyzing biopsy tissue expression of IGF- 1R, insulin&#xD;
           receptor, IGF-2 expression and phospho-YES expression, and through genomic sequencing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The pharmaceutical company discontinued availability of the drug and we were forced to close&#xD;
    the study before phase II was completed. Only one participant was enrolled on phase II.&#xD;
  </why_stopped>
  <start_date type="Actual">July 7, 2017</start_date>
  <completion_date type="Actual">October 16, 2021</completion_date>
  <primary_completion_date type="Actual">September 15, 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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)</measure>
    <time_frame>First 35 days of treatment</time_frame>
    <description>The safe dose or maximum tolerated dose (MTD) is defined as the dose level at which no more than 1 of up to 3-6 participants experience a dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of &lt; 5 days duration, grade 3 fever or infection &lt; 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib</measure>
    <time_frame>Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.</time_frame>
    <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase II: Number of Participants That is Without Progression at 4 Months</measure>
    <time_frame>At 4 months</time_frame>
    <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase II: Progression Free Survival (PFS) in Participants Receiving Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib</measure>
    <time_frame>Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.</time_frame>
    <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Number of Participants With Stable Disease &gt;= 6 Months as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in Participants Receiving Ganitumab With Dasatinib</measure>
    <time_frame>6 months</time_frame>
    <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (i.e., at least a 30% decrease in the sum of the diameters of target lesions) nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
    <description>Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
    <description>Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Phase I: Number of Participants With a Dose-Limiting Toxicity (DLT)</measure>
    <time_frame>First 35 days of treatment</time_frame>
    <description>A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of &lt; 5 days duration, grade 3 fever or infection &lt; 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
    <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Rhabdomyosarcoma</condition>
  <condition>Rhabdomyosarcoma, Alveolar</condition>
  <condition>Rhabdomyosarcoma, Embryonal</condition>
  <arm_group>
    <arm_group_label>Phase 1 Dose Level 1: Ganitumab and Dasatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase I Dose Level 1: Combination of ganitumab and dasatinib with limited dose escalation of dasatinib</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 1 Dose Level 2: Ganitumab and Dasatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase I Dose Level 2: Combination of ganitumab and dasatinib with limited dose escalation of dasatinib</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase 2 Dose Level 1: Ganitumab and Dasatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 2 Dose Level 1: Combination of ganitumab and dasatinib at the maximum tolerated dose (MTD) (or highest safe dose)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dasatinib</intervention_name>
    <description>Once daily on days -7 through day 27 during cycle 1, and then days 0-27 for subsequent cycles.</description>
    <arm_group_label>Phase 1 Dose Level 1: Ganitumab and Dasatinib</arm_group_label>
    <arm_group_label>Phase 2 Dose Level 1: Ganitumab and Dasatinib</arm_group_label>
    <other_name>Sprycel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dasatinib</intervention_name>
    <description>Twice daily on days -7 through day 27 during cycle 1, and then days 0-27 for subsequent cycles.</description>
    <arm_group_label>Phase 1 Dose Level 2: Ganitumab and Dasatinib</arm_group_label>
    <other_name>Sprycel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ganitumab</intervention_name>
    <description>Once every 2 weeks beginning on day 0.</description>
    <arm_group_label>Phase 1 Dose Level 1: Ganitumab and Dasatinib</arm_group_label>
    <arm_group_label>Phase 1 Dose Level 2: Ganitumab and Dasatinib</arm_group_label>
    <arm_group_label>Phase 2 Dose Level 1: Ganitumab and Dasatinib</arm_group_label>
    <other_name>Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients of any age must have histologically or cytologically confirmed embryonal or&#xD;
             alveolar rhabdomyosarcoma (RMS) confirmed by the Laboratory of Pathology, National&#xD;
             Cancer Institute (NCI) or by the Department of Pathology and Laboratory Medicine,&#xD;
             Children's Hospital Los Angeles (CHLA).&#xD;
&#xD;
          -  Patients must have measurable disease.&#xD;
&#xD;
          -  Patients must be able to undergo appropriate imaging studies to monitor tumor&#xD;
             response.&#xD;
&#xD;
          -  Archival tissue of tumors (slides or blocks (blocks preferred)) must be available for&#xD;
             analysis. If tissue is not available, patients willing to undergo a pre-treatment&#xD;
             biopsy may enroll.&#xD;
&#xD;
          -  Prior Therapies:&#xD;
&#xD;
               -  There is no maximum number of prior medical therapies.&#xD;
&#xD;
               -  There must be no curative or life prolonging treatments available.&#xD;
&#xD;
               -  Patients who have received other insulin-like growth factor 1 receptor (IGF-1R)&#xD;
                  antibodies or inhibitors are eligible, as long as an appropriate washout period&#xD;
                  has elapsed (see below).&#xD;
&#xD;
               -  Participants must have had their last fraction of external beam radiation therapy&#xD;
                  that is local and palliative at least 2 weeks prior to enrollment (except for&#xD;
                  radiation therapy to the lungs as noted below) and had their last substantial&#xD;
                  bone marrow radiation at least 6 weeks prior to enrollment.&#xD;
&#xD;
               -  Participants must have had their last radiation therapy of the lungs at least 8&#xD;
                  weeks prior to enrollment.&#xD;
&#xD;
               -  Participants must have had their last dose of temozolomide at least 4 weeks prior&#xD;
                  to enrollment; their last dose of other cytotoxic chemotherapy at least 3 weeks&#xD;
                  prior to enrollment; their last dose of biological therapy, such as biological&#xD;
                  response modifiers (e.g., cytokines), immunomodulatory agents, vaccines,&#xD;
                  differentiating agents, used to treat their cancer at least 7 days prior to&#xD;
                  enrollment, their last dose of a monoclonal antibody the shorter of 3 half- lives&#xD;
                  or 28 days prior to enrollment, and their last dose of any investigational agent&#xD;
                  at least 4 weeks prior to enrollment.&#xD;
&#xD;
               -  Participants must have recovered from the acute toxic effects of prior therapy to&#xD;
                  a grade 1 (Common Terminology Criteria for Adverse Events (CTCAE) v.5.0) level&#xD;
                  prior to enrollment (does not apply to alopecia).&#xD;
&#xD;
          -  Age. There are no age limits for this study, but patients must have the ability to&#xD;
             swallow tablets.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2&#xD;
             or Karnofsky &gt;50% (if greater than or equal to 16 years of age); or children &lt; 16&#xD;
             years old must have a Lansky performance of greater than or equal to 50%.&#xD;
&#xD;
          -  Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  absolute neutrophil count greater than or equal to 1,000/mcL&#xD;
&#xD;
               -  platelets greater than or equal to 75,000/mcL&#xD;
&#xD;
               -  total bilirubin less than or equal to 1.5X upper limit of normal (ULN), with&#xD;
                  exception of patients with Gilbert syndrome&#xD;
&#xD;
               -  Alanine aminotransferase (ALT) less than or equal to 3.0X upper limit of normal&#xD;
                  (ULN)&#xD;
&#xD;
               -  creatinine within normal institutional limits OR creatinine clearance greater&#xD;
                  than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above&#xD;
                  institutional normal.&#xD;
&#xD;
               -  Normal blood glucose for age&#xD;
&#xD;
          -  Hematologic parameters for patients undergoing biopsy only: Patients should have INR&#xD;
             less than or equal to 1.4 and prothrombin time (PT) less than or equal to 40 seconds&#xD;
             (unless due to lupus anticoagulant). In patients not meeting these parameters,&#xD;
             clearance by hematology will be required prior to undergoing a biopsy.&#xD;
&#xD;
          -  Cardiac Function: corrected Q-T interval (QTc) &lt; 480 msec, and ejection fraction&#xD;
             greater than or equal to 50%&#xD;
&#xD;
          -  Contraception. The effects of these agents on the developing human fetus are unknown.&#xD;
             For this reason, men and women of child-bearing potential must agree to use adequate&#xD;
             contraception (hormonal or barrier method of birth control; abstinence) prior to study&#xD;
             entry, for the duration of study participation, and for 4 months after completion of&#xD;
             administration of either agent. Should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, she should inform&#xD;
             her treating physician immediately. Negative pregnancy test is required for women of&#xD;
             childbearing potential.&#xD;
&#xD;
          -  Ability of subject or Legally Authorized Representative (LAR)) to understand and the&#xD;
             willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Patients will be strongly encouraged to participate in 10-C-0086. If a patient does&#xD;
             not agree to enroll on 10-C-0086, germline genetic analysis will not be performed.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents.&#xD;
&#xD;
          -  Patients with known brain metastases should be excluded from this clinical trial&#xD;
             because of their poor prognosis and because they often develop progressive neurologic&#xD;
             dysfunction that would confound the evaluation of neurologic and other adverse events.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to dasatinib or ganitumab or other agents used in study.&#xD;
&#xD;
          -  Patients who require concurrent treatment with any medications or substances that are&#xD;
             potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) are ineligible. Because&#xD;
             the lists of these agents are constantly changing, it is important to regularly&#xD;
             consult a frequently updated list, or medical reference text such as the Physician's&#xD;
             Desk Reference. As part of the enrollment/informed consent procedures, the patient&#xD;
             will be counseled on the risk of interactions with other agents, and what to do if new&#xD;
             medications need to be prescribed or if the patient is considering a new&#xD;
             over-the-counter medicine or herbal product.&#xD;
&#xD;
          -  Patients who require concurrent treatment with antithrombotic and/or anti-platelet&#xD;
             agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, and/or&#xD;
             ibuprofen).&#xD;
&#xD;
          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an&#xD;
             inability to take oral medication or a requirement for intravenous (IV) alimentation r&#xD;
             surgical procedures affecting absorption, or active peptic ulcer disease) that impairs&#xD;
             their ability to swallow and retain dasatinib tablets are excluded.&#xD;
&#xD;
          -  Patients with a history of radiation pneumonitis.&#xD;
&#xD;
          -  Patients may not have any clinically significant cardiovascular disease including the&#xD;
             following:&#xD;
&#xD;
               -  myocardial infarction or ventricular tachyarrhythmia within 6 months&#xD;
&#xD;
               -  major conduction abnormality (unless a cardiac pacemaker is present).&#xD;
&#xD;
        Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath,&#xD;
        chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress&#xD;
        test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation. The&#xD;
        patient may be referred to a cardiologist at the discretion of the principal investigator.&#xD;
        Patients with underlying cardiopulmonary dysfunction should be excluded from the study.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, the following:&#xD;
             ongoing or active infection; history of significant bleeding disorder, including&#xD;
             congenital (von Willebrands disease) or acquired (anti-factor VIII antibodies)&#xD;
             disorders; large pleural effusions; or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements.&#xD;
&#xD;
          -  Patients with known pre-existing diabetes mellitus will be excluded because of the&#xD;
             risk of hyperglycemia with ganitumab.&#xD;
&#xD;
          -  Pregnant women are excluded from this study because animal studies with dasatinib have&#xD;
             shown embryolethality and fetal skeletal alterations at non-toxic maternal doses.&#xD;
             Because there is an unknown but potential risk for adverse events in nursing human&#xD;
             infants secondary to treatment of the mother with dasatinib, breastfeeding should be&#xD;
             discontinued if the mother is treated with dasatinib.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christine M Heske, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute (NCI)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90054-0700</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-C-0049.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <results_first_submitted>March 17, 2022</results_first_submitted>
  <results_first_submitted_qc>March 17, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 14, 2022</results_first_posted>
  <last_update_submitted>March 17, 2022</last_update_submitted>
  <last_update_submitted_qc>March 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Institute (NCI)</investigator_affiliation>
    <investigator_full_name>Christine Heske, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>ERMS</keyword>
  <keyword>ARMS</keyword>
  <keyword>Monoclonal Antibody</keyword>
  <keyword>YES</keyword>
  <keyword>RMS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma, Alveolar</mesh_term>
    <mesh_term>Rhabdomyosarcoma, Embryonal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dasatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Clinical data available during the study and indefinitely.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).</ipd_time_frame>
    <ipd_access_criteria>Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Requests for all collected individual participant data (IPD) data from clinical trials, conducted under a binding collaborative agreement between National Cancer Institute (NCI)/Division of Cancer Treatment and Diagnosis (DCTD) and a pharmaceutical/biotechnology company, that are not under data safety monitoring board (DSMB) monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) Director in conjunction with the NCI/DCTD Regulatory Affairs Branch).</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 6, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT03041701/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 13, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT03041701/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
          <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="P2">
          <title>Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg</title>
          <description>Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="P3">
          <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
          <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Ph I: Dose Level 1 and 2 Dose Escalation</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Not evaluable for toxicity</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Ph 2:Dose Level 1 Maximum Tolerated Dose</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </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_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Unacceptable further treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
          <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="B2">
          <title>Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg</title>
          <description>Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="B3">
          <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
          <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="B4">
          <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="7"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.71" spread="5.15"/>
                    <measurement group_id="B2" value="20.17" spread="8.18"/>
                    <measurement group_id="B3" value="5" spread="0"/>
                    <measurement group_id="B4" value="15.86" spread="7.62"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ethnicity unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Race unknown</title>
              <category_list>
                <category>
                  <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_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White + Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)</title>
        <description>The safe dose or maximum tolerated dose (MTD) is defined as the dose level at which no more than 1 of up to 3-6 participants experience a dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of &lt; 5 days duration, grade 3 fever or infection &lt; 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.</description>
        <time_frame>First 35 days of treatment</time_frame>
        <population>Dasatinib MTD schedule is daily.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)</title>
          <description>The safe dose or maximum tolerated dose (MTD) is defined as the dose level at which no more than 1 of up to 3-6 participants experience a dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of &lt; 5 days duration, grade 3 fever or infection &lt; 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.</description>
          <population>Dasatinib MTD schedule is daily.</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="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib</title>
        <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.</description>
        <time_frame>Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.</time_frame>
        <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
            <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib</title>
          <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.</description>
          <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</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="5"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase II: Number of Participants That is Without Progression at 4 Months</title>
        <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
        <time_frame>At 4 months</time_frame>
        <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
            <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Number of Participants That is Without Progression at 4 Months</title>
          <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
          <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</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="5"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II: Progression Free Survival (PFS) in Participants Receiving Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib</title>
        <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
        <time_frame>Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.</time_frame>
        <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
            <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Progression Free Survival (PFS) in Participants Receiving Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib</title>
          <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
          <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.93" lower_limit="1.67" upper_limit="5.83"/>
                    <measurement group_id="O2" value="0.88" lower_limit="NA" upper_limit="NA">Full range cannot be determined for one participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II: Number of Participants With Stable Disease &gt;= 6 Months as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in Participants Receiving Ganitumab With Dasatinib</title>
        <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (i.e., at least a 30% decrease in the sum of the diameters of target lesions) nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
        <time_frame>6 months</time_frame>
        <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
            <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Number of Participants With Stable Disease &gt;= 6 Months as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in Participants Receiving Ganitumab With Dasatinib</title>
          <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (i.e., at least a 30% decrease in the sum of the diameters of target lesions) nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.</description>
          <population>Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.</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="5"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib</title>
        <description>Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib</title>
          <description>Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3 related to ganitumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 related to ganitumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 related to ganitumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 related to dasatinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 related to dasatinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 related to dasatinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib</title>
        <description>Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
            <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib</title>
          <description>Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 3 related to ganitumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 related to ganitumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 related to ganitumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 related to dasatinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4 related to dasatinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5 related to dasatinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Phase I: Number of Participants With a Dose-Limiting Toxicity (DLT)</title>
        <description>A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of &lt; 5 days duration, grade 3 fever or infection &lt; 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.</description>
        <time_frame>First 35 days of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Phase I: Number of Participants With a Dose-Limiting Toxicity (DLT)</title>
          <description>A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of &lt; 5 days duration, grade 3 fever or infection &lt; 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)</title>
        <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O2">
            <title>Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg</title>
            <description>Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
          <group group_id="O3">
            <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
            <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)</title>
          <description>Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg</title>
          <description>Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="E2">
          <title>Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg</title>
          <description>Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
        <group group_id="E3">
          <title>Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg</title>
          <description>Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0.&#xD;
Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</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="2" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, Blood culture positive for Klebsiella pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Hyponatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, tumor hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchopulmonary hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</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="7" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="31" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" events="25" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" events="4" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Tricuspid valve disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, Left eye/ medial SCH-Irritation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Colonic obstruction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Mild tenderness in lower right quadrant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Gagging</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Lower lip pressure ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Oral bleeding</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrointestinal disorders - Other, Oral ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ileus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="11" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="8" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="12" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="14" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, Difficulty with accessing port</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, Specify</sub_title>
                <description>Pain associated with nephrostomy tube placement</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, Superficial edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions-Other, pain associated with suprapubic catheter</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lip infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Soft tissue infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Tracheitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Burn</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="11" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="14" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cardiac troponin T increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cholesterol high</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="15" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" events="22" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lymphocyte count increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="17" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" events="12" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="12" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="10" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypermagnesemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="14" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="16" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="17" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="11" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" events="9" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="6" subjects_at_risk="7"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Appetite decrease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Appetite slight decrease</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Decrease in appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Hyperphosphatemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Metabolism and nutrition disorders - Other, Vitamin D deficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="9" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chest wall pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, Specify</sub_title>
                <description>Tenderness to palpation over posterior lower left ribs</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, Specify</sub_title>
                <description>Tenderness to palpation right upper back and lateral chest</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Tumor hemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, Panic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, Restless legs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Psychiatric disorders - Other, Sleep disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hemoglobinuria</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="15" subjects_affected="7" subjects_at_risk="7"/>
                <counts group_id="E2" events="9" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, Dysuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, Mild suprapubic distention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Renal and urinary disorders - Other, White blood cell, Urine increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="21" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="14" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Airway obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Choking</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Hemoptysis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Hypoxemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, L nasal fullness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Some congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, Tachypnea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Photosensitivity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="7"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Candida diaper rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Diaper rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Erythema/ pressure sore L.buttock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, Insect bites</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, Pain lateral of port access</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </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>Dr. Christine Heske</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>240-760-6197</phone>
      <email>christine.heske@nih.gov</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/NCT03041701
org study id: 170049
secondary id: 17-C-0049
nct id: NCT03041701
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Background:

      Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Two types are
      embryonal RMS (ERMS) and alveolar RMS (ARMS). Dasatinib may block over-expression of a
      certain enzyme. Ganitumab may block a certain growth factor, which might suppress tumor
      growth. This drug combination may help slow tumor growth in people with ERMS and ARMS.

      Objective:

      To see if dasatinib combined with ganitumab is safe and shrinks or slows the growth of tumors
      in people with ERMS and ARMS.

      Eligibility:

      People any age who have ERMS or ARMS that did not respond to previous treatment and who can
      swallow tablets

      Design:

      Participants will be screened with:

        -  Medical history

        -  Physical exam

        -  Blood, urine, and heart tests

        -  Scans/x-rays

        -  Tissue sample: This can be from previous surgery or biopsy.

        -  Optional biopsy: A small piece of the tumor is removed with a needle.

      Participants will be asked to co-enroll in another protocol.

      Participants will get a drug interaction handout and wallet card that show what foods and
      medications to avoid.

      Participants will be treated in cycles. The first cycle is 35 days, and the rest are 28 days.
      Participants will take dasatinib by mouth daily. They will get ganitumab through an
      intravenous (IV) every 2 weeks. They will have a physical exam every 1-2 weeks, and urine and
      heart tests before most cycles.

      Participants will continue treatment as long as they do not have severe side effects, or
      their tumors do not get worse.

      After ending treatment, participants will have a visit. This includes repeats of the
      screening tests.
Background:

        -  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. The annual
           incidence in the United States is 4-7 cases per million children under 15 years, which
           represents 250 new cases per year. Two major histologic subtypes exist: embryonal
           rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS), the latter of which
           carries a particularly poor prognosis.

        -  Over-expression of both the type like growth factor 1 (1 IGF) receptor insulin-like
           growth factor type 1 receptor (IGF-1R) and its ligands has been observed in multiple
           malignancies, including pediatric sarcomas, and abnormal activation of this pathway
           contributes to sarcoma development and progression. Downstream signaling cascades of
           IGF-1R further regulate tumor cell proliferation, survival, and metastasis through the
           mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK)
           and phosphatidylinositol 3-kinases (PI3Ks)/mammalian target of rapamycin (mTOR)
           pathways. In the majority of RMS, IGF-1R is highly expressed.

        -  Monoclonal antibodies targeting IGF-1R interfere with ligand binding and decrease the
           expression of the receptor on cell surfaces by internalization and degradation of the
           receptor. A number of these have been tested in the clinical setting. Results from a
           phase II trial using monotherapy with monoclonal antibodies against IGF-1R resulted in
           clinically meaningful responses in about 10-15% of patients with RMS. However, the vast
           majority of these responses were short-lived with a rapid onset of resistance.

        -  YES is a member of the SRC family tyrosine kinases (SFKs), non-receptor tyrosine kinases
           that function in a number of signaling pathways necessary for cell growth,
           differentiation and survival. Preclinical work suggests involvement of YES in a number
           of solid tumor types, including colon carcinoma, oral squamous cell carcinoma, glioma,
           pancreatic cancer, mesothelioma, and RMS.

        -  Recently, the Helman lab published preclinical work showing that in both embryonal and
           alveolar RMS models, blockade of IGF-1R results in YES activation and that YES
           activation is associated with resistance to IGF-1R blockade. In addition, combination
           blockade of IGF-1R and YES in vitro results in downregulation of phospho-AKT in some
           cell lines. Treatment blocking both IGF-1R and YES results in enhanced growth inhibition
           of multiple cell lines of both embryonal and alveolar RMS in vitro and in vivo.

      Objectives:

        1. Phase I: To determine the safe dose of dasatinib when given with ganitumab in patients
           with relapsed or refractory embryonal or alveolar RMS.

        2. Phase II: To determine if the use of ganitumab plus dasatinib is able to be associated
           with a modest fraction of patients who experience an objective clinical response
           (complete response (CR) and partial response (PR) as defined by Response Evaluation
           Criteria in Solid Tumors (RECIST) criteria. In addition, a second primary objective will
           estimate the fraction that is without progression at 4 months.

      Eligibility:

        -  Patients must have a diagnosis of relapsed or refractory embryonal or alveolar RMS, be
           able to swallow tablets, have archival tissue available.

        -  Patients must have adequate performance status and adequate major organ function and
           have recovered from acute toxicity of all prior therapies.

      Design:

        -  This is an open label, multi-site, phase I/II study designed to determine if ganitumab
           given in combination with dasatinib in children and adults with relapsed or refractory
           embryonal or alveolar RMS for whom no curative options exist.

        -  In the phase I portion, using a standard 3 + 3 design, limited dose escalations will be
           performed to define the maximum tolerated dose (MTD) or the highest safe dose tested of
           dasatinib when given in combination with ganitumab in this patient population.

        -  In the phase II component, sixteen (16) evaluable patients, including up to 6 patients
           from the phase I portion treated at the selected phase II dose, will be enrolled to rule
           out a 5% fraction with a clinical response in favor of a 30% fraction with a clinical
           response, using a one sided 0.10 significance level exact test for a binomial
           proportion. In practice, the fraction of the 16 patients that have objective responses
           will be determined and reported along with 80% and 95% confidence intervals. If there
           are 3 objective responses in 16 evaluable patients, the lower one-sided exact 90%
           confidence interval is 7.1%, thus ruling out 5%.

        -  It is anticipated that approximately 10-15 patients per year may be accrued onto this
           trial. Thus, 2 to 3 years is expected to completed accrual.

        -  In all patients, mechanisms of response and resistance will be assessed by analyzing
           archival tissue for expression of IGF-1R, insulin receptor, IGF-2 expression and
           phospho-YES expression, and through genomic sequencing (on protocol 10-C-0086). Genomic
           sequencing of tumor cells from tissue relative to non-tumor cells from whole blood will
           be profiled to identify the genomic variances that may contribute to response or disease
           progression and provide an understanding of molecular abnormalities. Ribonucleic acid
           (RNA) sequencing will be conducted to provide expression data and give relevance to
           deoxyribonucleic acid (DNA) mutations; Quantitative proteomics analysis will be
           conducted on all patients to determine the exact amounts of specific proteins and/or to
           confirm expression of genes that are correlative of response and disease progression.
           Genomic and transcriptomic analysis will be conducted on patients who consent to
           protocol 10-C-0086, Comprehensive Omics Analysis of Pediatric Solid Tumors and
           Establishment of a Repository for Related Biological Studies. All genomic,
           transcriptomic, and proteomic molecular analyses will be retrospective and exploratory.

        -  In patients who agree to undergo biopsy of their tumor, provided the tissue is easily
           accessible and can be biopsied safely with minimal morbidity, mechanisms of response and
           resistance will be assessed by analyzing biopsy tissue expression of IGF- 1R, insulin
           receptor, IGF-2 expression and phospho-YES expression, and through genomic sequencing.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)
time frame: First 35 days of treatment
description: The safe dose or maximum tolerated dose (MTD) is defined as the dose level at which no more than 1 of up to 3-6 participants experience a dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of < 5 days duration, grade 3 fever or infection < 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.
measure: Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib
time frame: Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.
description: Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
measure: Phase II: Number of Participants That is Without Progression at 4 Months
time frame: At 4 months
description: Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.
measure: Phase II: Progression Free Survival (PFS) in Participants Receiving Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib
time frame: Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.
description: PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.
measure: Phase II: Number of Participants With Stable Disease >= 6 Months as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in Participants Receiving Ganitumab With Dasatinib
time frame: 6 months
description: Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (i.e., at least a 30% decrease in the sum of the diameters of target lesions) nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.
measure: Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib
time frame: Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
description: Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
measure: Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib
time frame: Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
description: Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
measure: Phase I: Number of Participants With a Dose-Limiting Toxicity (DLT)
time frame: First 35 days of treatment
description: A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of < 5 days duration, grade 3 fever or infection < 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.
measure: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
time frame: Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
description: Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
arm group label: Phase 1 Dose Level 1: Ganitumab and Dasatinib
arm group type: Experimental
description: Phase I Dose Level 1: Combination of ganitumab and dasatinib with limited dose escalation of dasatinib
arm group label: Phase 1 Dose Level 2: Ganitumab and Dasatinib
arm group type: Experimental
description: Phase I Dose Level 2: Combination of ganitumab and dasatinib with limited dose escalation of dasatinib
arm group label: Phase 2 Dose Level 1: Ganitumab and Dasatinib
arm group type: Experimental
description: Phase 2 Dose Level 1: Combination of ganitumab and dasatinib at the maximum tolerated dose (MTD) (or highest safe dose)
intervention type: Drug
intervention name: Dasatinib
description: Once daily on days -7 through day 27 during cycle 1, and then days 0-27 for subsequent cycles.
arm group label: Phase 1 Dose Level 1: Ganitumab and Dasatinib
arm group label: Phase 2 Dose Level 1: Ganitumab and Dasatinib
other name: Sprycel
intervention type: Drug
intervention name: Dasatinib
description: Twice daily on days -7 through day 27 during cycle 1, and then days 0-27 for subsequent cycles.
arm group label: Phase 1 Dose Level 2: Ganitumab and Dasatinib
other name: Sprycel
intervention type: Drug
intervention name: Ganitumab
description: Once every 2 weeks beginning on day 0.
arm group label: Phase 1 Dose Level 1: Ganitumab and Dasatinib
arm group label: Phase 1 Dose Level 2: Ganitumab and Dasatinib
arm group label: Phase 2 Dose Level 1: Ganitumab and Dasatinib
other name: Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479
criteria: 
gender: All
minimum age: 2 Years
maximum age: N/A
healthy volunteers: No
last name: Christine M Heske, M.D.
role: Principal Investigator
affiliation: National Cancer Institute (NCI)
facility: 
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-C-0049.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Principal Investigator
investigator affiliation: National Cancer Institute (NCI)
investigator full name: Christine Heske, M.D.
investigator title: Principal Investigator
mesh term: Rhabdomyosarcoma
mesh term: Rhabdomyosarcoma, Alveolar
mesh term: Rhabdomyosarcoma, Embryonal
mesh term: Dasatinib
sharing ipd: Yes
ipd description: Clinical data available during the study and indefinitely.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
ipd access criteria: Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Requests for all collected individual participant data (IPD) data from clinical trials, conducted under a binding collaborative agreement between National Cancer Institute (NCI)/Division of Cancer Treatment and Diagnosis (DCTD) and a pharmaceutical/biotechnology company, that are not under data safety monitoring board (DSMB) monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) Director in conjunction with the NCI/DCTD Regulatory Affairs Branch).
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 