<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/NCT02202746</url>
  </required_header>
  <id_info>
    <org_study_id>CO-3810-025</org_study_id>
    <nct_id>NCT02202746</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer</brief_title>
  <official_title>A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral Lucitanib in Patients With FGF Aberrant Metastatic Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clovis Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Clovis Oncology, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether lucitanib is safe and effective in the&#xD;
      treatment of patients with FGF aberrant metastatic breast cancer, as well as in the treatment&#xD;
      of patients with biomarker negative (FGF non-aberrant) metastatic breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3,&#xD;
      VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.&#xD;
&#xD;
      The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can&#xD;
      provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or&#xD;
      FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in patients&#xD;
      not known to have FGF abnormalities.&#xD;
&#xD;
      Based on these results, this study is designed to explore the safety and anti-tumor activity&#xD;
      of daily lucitanib in breast cancer patients with and without alterations of the FGF pathway.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision to end monotherapy development of the compound in breast cancer.&#xD;
  </why_stopped>
  <start_date type="Actual">September 9, 2014</start_date>
  <completion_date type="Actual">January 18, 2017</completion_date>
  <primary_completion_date type="Actual">January 17, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator</measure>
    <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
    <description>The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) by RECIST v1.1</measure>
    <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
    <description>ORR is the percentage of patients with a best response of CR or PR according to RECIST v1.1. The best response is recorded from the start of the treatment (Day 1) until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DR) by RECIST v1.1</measure>
    <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
    <description>DR for complete response (CR) and partial response (PR) was measured from the date that any of these best confirmed responses was first recorded until the first date that PD was objectively documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) by RECIST v1.1</measure>
    <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
    <description>The DCR is defined as the percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax</measure>
    <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
    <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Cmax = maximum concentration following administration of lucitanib.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax</measure>
    <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
    <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Tmax = time to maximum concentration following administration of lucitanib</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast</measure>
    <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
    <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUClast = area under the plasma concentration time curve from time 0 to the last quantifiable time point (24 hour)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf</measure>
    <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
    <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUCinf = area under the plasma concentration time curve from 0 to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf</measure>
    <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
    <description>Relative bioavailability of lucitanib was evaluated by comparison of (log-transformed) AUClast, Cmax and AUCinf of the tablet formulation to the capsule formulation using an analysis of variance (ANOVA) model with treatment as a fixed effect. The geometric means, ratio of the geometric means and 90% confidence intervals (CI) on the ratio of Tablet to Capsule (T:R) were presented for AUClast, Cmax and AUCinf. The CIs on the ratio of untransformed PK parameters were derived through reverse transformation of the 90% CI of the difference in the log scale to the 90% CI of the ratio in the original scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Cycle 1 Day 1 to date of death, assessed up to 29 months</time_frame>
    <description>Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score</measure>
    <time_frame>From Cycle 1 Day 1 until end of treatment, assessed up to 29 months</time_frame>
    <description>FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 37 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (10 items) ranging from 0 to 40; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. FACT-B Total Score is derived from adding the five subscale scores. Total possible score ranges from 0 to 148. High scale score represents a better QoL.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">178</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Metastatic Breast Cancer</condition>
  <condition>MBC</condition>
  <condition>HER2 Positive</condition>
  <condition>HER2</condition>
  <condition>Estrogen Receptor Positive</condition>
  <condition>ER</condition>
  <condition>Triple Negative</condition>
  <arm_group>
    <arm_group_label>Cohort A: Lucitanib (CO-3810) 10 mg daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B: Lucitanib (CO-3810) 15 mg daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C: Lucitanib (CO-3810) 10 mg daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lucitanib</intervention_name>
    <description>Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1-3), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)</description>
    <arm_group_label>Cohort A: Lucitanib (CO-3810) 10 mg daily</arm_group_label>
    <arm_group_label>Cohort B: Lucitanib (CO-3810) 15 mg daily</arm_group_label>
    <arm_group_label>Cohort C: Lucitanib (CO-3810) 10 mg daily</arm_group_label>
    <other_name>CO-3810</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed metastatic breast cancer relapsed or&#xD;
             refractory to approved standard available treatment&#xD;
&#xD;
          -  Prior treatment with standard first line therapy in the metastatic setting&#xD;
&#xD;
          -  Availability of tumor tissue sufficient for confirmatory testing of FGFR1 and 11q&#xD;
             amplification status&#xD;
&#xD;
          -  Demonstrated progression of disease by radiological or clinical assessment (Measurable&#xD;
             disease according to RECIST Version 1.1 is NOT required for enrollment)&#xD;
&#xD;
          -  Estimated life expectancy &gt;6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or recent treatment with biologic anticancer therapies&#xD;
&#xD;
          -  Ongoing AEs from prior anticancer therapies&#xD;
&#xD;
          -  Active central nervous system (CNS) metastases&#xD;
&#xD;
          -  Clinically significant or uncontrolled hypertension or cardiac disease&#xD;
&#xD;
          -  Females who are pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Arizona Oncology Associates</name>
      <address>
        <city>Sedona</city>
        <state>Arizona</state>
        <zip>86336</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Blood and Cancer Center</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Jude Heritage Medical Center</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moores UCSD Cancer Center</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Associates Medical Group, Inc.</name>
      <address>
        <city>Redondo Beach</city>
        <state>California</state>
        <zip>90277</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Coast Medical Oncology Group</name>
      <address>
        <city>Santa Maria</city>
        <state>California</state>
        <zip>93454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial West Cancer Center</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University, Robert H. Lurie Comprehensive Cancer Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizon Oncology Center</name>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <zip>47905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Sidney Kimmel Comprehensive Cancer Center at John Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cooper University Hospital</name>
      <address>
        <city>Voorhees</city>
        <state>New Jersey</state>
        <zip>08043</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sciode Medical Associates, PLLC</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10469</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Breast Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Austin Central</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Cancer and Blood Disorders</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US Oncology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Oncology Associates</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <results_first_submitted>February 20, 2020</results_first_submitted>
  <results_first_submitted_qc>June 20, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 23, 2020</results_first_posted>
  <disposition_first_submitted>August 5, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>August 5, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 12, 2019</disposition_first_posted>
  <last_update_submitted>June 20, 2020</last_update_submitted>
  <last_update_submitted_qc>June 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast cancer</keyword>
  <keyword>Metastatic breast cancer</keyword>
  <keyword>MBC</keyword>
  <keyword>HER2 positive</keyword>
  <keyword>HER2+</keyword>
  <keyword>Estrogen receptor positive</keyword>
  <keyword>ER+</keyword>
  <keyword>Triple negative</keyword>
  <keyword>FGFR1</keyword>
  <keyword>11q</keyword>
  <keyword>FGF aberrant</keyword>
  <keyword>Biomarker negative</keyword>
  <keyword>FGF non-aberrant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 27, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT02202746/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/46/NCT02202746/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>178 patients were recruited from 32 sites in the United States.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Lucitanib (CO-3810) 10 mg QD</title>
          <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
        </group>
        <group group_id="P2">
          <title>Lucitanib (CO-3810) 15 mg QD</title>
          <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="109"/>
                <participants group_id="P2" count="69"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="109"/>
                <participants group_id="P2" count="69"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lucitanib (CO-3810) 10 mg QD</title>
          <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
        </group>
        <group group_id="B2">
          <title>Lucitanib (CO-3810) 15 mg QD</title>
          <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
        </group>
        <group group_id="B3">
          <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="109"/>
            <count group_id="B2" value="69"/>
            <count group_id="B3" value="178"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.0" lower_limit="27" upper_limit="82"/>
                    <measurement group_id="B2" value="53.0" lower_limit="27" upper_limit="80"/>
                    <measurement group_id="B3" value="55.0" lower_limit="27" upper_limit="82"/>
                  </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="109"/>
                    <measurement group_id="B2" value="67"/>
                    <measurement group_id="B3" value="176"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </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>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="87"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="148"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not provided</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown/Not assessed</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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 or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Hispanic or Latino</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="97"/>
                    <measurement group_id="B2" value="61"/>
                    <measurement group_id="B3" value="158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not Provided</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Prior Anticancer Therapies</title>
          <units>Therapies</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.0" lower_limit="1" upper_limit="18"/>
                    <measurement group_id="B2" value="6.0" lower_limit="1" upper_limit="16"/>
                    <measurement group_id="B3" value="6.0" lower_limit="1" upper_limit="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fibroblast Growth Factor (FGF) Status</title>
          <description>FGFR1 and 11q are genes that are amplified in a percentage of breast cancers. Sites were required to submit archival tumor specimens for all enrolled patients for central laboratory confirmation of FGFR1 or 11q amplification status. Patients were categorized based on results indicating FGFR1 amplification, 11q amplification, both FGFR1 and 11q amplification, or non-amplification of either gene (negative).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>11q</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGFR1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FGFR1 &amp; 11q</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator</title>
        <description>The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.</description>
        <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
        <population>Efficacy population: all patients who have received at least one dose of lucitanib and are confirmed as FGR1-, 11q-amplified, or FGF non-amplified per the central laboratory</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator</title>
          <description>The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.</description>
          <population>Efficacy population: all patients who have received at least one dose of lucitanib and are confirmed as FGR1-, 11q-amplified, or FGF non-amplified per the central laboratory</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="67"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93" lower_limit="78" upper_limit="140"/>
                    <measurement group_id="O2" value="77" lower_limit="50" upper_limit="86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response Rate (ORR) by RECIST v1.1</title>
        <description>ORR is the percentage of patients with a best response of CR or PR according to RECIST v1.1. The best response is recorded from the start of the treatment (Day 1) until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.</description>
        <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
        <population>Efficacy population: all patients who have received at least one dose of lucitanib and are confirmed as FGR1-, 11q-amplified, or FGF non-amplified per the central laboratory</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O3">
            <title>All Patients</title>
            <description>The total efficacy population analyzed for response</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) by RECIST v1.1</title>
          <description>ORR is the percentage of patients with a best response of CR or PR according to RECIST v1.1. The best response is recorded from the start of the treatment (Day 1) until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.</description>
          <population>Efficacy population: all patients who have received at least one dose of lucitanib and are confirmed as FGR1-, 11q-amplified, or FGF non-amplified per the central laboratory</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7"/>
                    <measurement group_id="O2" value="1.5"/>
                    <measurement group_id="O3" value="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DR) by RECIST v1.1</title>
        <description>DR for complete response (CR) and partial response (PR) was measured from the date that any of these best confirmed responses was first recorded until the first date that PD was objectively documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.</description>
        <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
        <population>Efficacy population for patients who had a confirmed CR or PR</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DR) by RECIST v1.1</title>
          <description>DR for complete response (CR) and partial response (PR) was measured from the date that any of these best confirmed responses was first recorded until the first date that PD was objectively documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.</description>
          <population>Efficacy population for patients who had a confirmed CR or PR</population>
          <units>Days</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="175" lower_limit="44" upper_limit="209"/>
                    <measurement group_id="O2" value="336" lower_limit="336" upper_limit="336"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR) by RECIST v1.1</title>
        <description>The DCR is defined as the percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.</description>
        <time_frame>From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months</time_frame>
        <population>Efficacy population only</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O3">
            <title>All Patients</title>
            <description>The total efficacy population analyzed for response</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR) by RECIST v1.1</title>
          <description>The DCR is defined as the percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt; 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.</description>
          <population>Efficacy population only</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="106"/>
                <count group_id="O2" value="67"/>
                <count group_id="O3" value="173"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.1"/>
                    <measurement group_id="O2" value="34.3"/>
                    <measurement group_id="O3" value="42.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax</title>
        <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Cmax = maximum concentration following administration of lucitanib.</description>
        <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
        <population>PK parameters were assessed in a subset of patients (N=15)</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib tablet or capsule given orally</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib tablet or capsule given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax</title>
          <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Cmax = maximum concentration following administration of lucitanib.</description>
          <population>PK parameters were assessed in a subset of patients (N=15)</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tablet</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="292" spread="156"/>
                    <measurement group_id="O2" value="278" spread="99.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Capsule</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="265" spread="137"/>
                    <measurement group_id="O2" value="285" spread="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax</title>
        <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Tmax = time to maximum concentration following administration of lucitanib</description>
        <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
        <population>PK parameters were assessed in a subset of patients (N=15)</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib tablet or capsule given orally</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib tablet or capsule given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax</title>
          <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Tmax = time to maximum concentration following administration of lucitanib</description>
          <population>PK parameters were assessed in a subset of patients (N=15)</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tablet</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.5" upper_limit="4.0"/>
                    <measurement group_id="O2" value="1.0" lower_limit="0.5" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Capsule</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" lower_limit="1.0" upper_limit="4.0"/>
                    <measurement group_id="O2" value="1.0" lower_limit="1.0" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast</title>
        <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUClast = area under the plasma concentration time curve from time 0 to the last quantifiable time point (24 hour)</description>
        <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
        <population>PK parameters were assessed in a subset of patients (N=15)</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib tablet or capsule given orally</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib tablet or capsule given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast</title>
          <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUClast = area under the plasma concentration time curve from time 0 to the last quantifiable time point (24 hour)</description>
          <population>PK parameters were assessed in a subset of patients (N=15)</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tablet</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2550" spread="1150"/>
                    <measurement group_id="O2" value="2840" spread="1230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Capsule</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2650" spread="1380"/>
                    <measurement group_id="O2" value="2420" spread="613"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf</title>
        <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUCinf = area under the plasma concentration time curve from 0 to infinity</description>
        <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
        <population>PK parameters were assessed in a subset of patients (N=15)</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib tablet or capsule given orally</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib tablet or capsule given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf</title>
          <description>The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUCinf = area under the plasma concentration time curve from 0 to infinity</description>
          <population>PK parameters were assessed in a subset of patients (N=15)</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tablet</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4780" spread="2140"/>
                    <measurement group_id="O2" value="5720" spread="3760"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Capsule</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5680" spread="2730"/>
                    <measurement group_id="O2" value="4620" spread="1620"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf</title>
        <description>Relative bioavailability of lucitanib was evaluated by comparison of (log-transformed) AUClast, Cmax and AUCinf of the tablet formulation to the capsule formulation using an analysis of variance (ANOVA) model with treatment as a fixed effect. The geometric means, ratio of the geometric means and 90% confidence intervals (CI) on the ratio of Tablet to Capsule (T:R) were presented for AUClast, Cmax and AUCinf. The CIs on the ratio of untransformed PK parameters were derived through reverse transformation of the 90% CI of the difference in the log scale to the 90% CI of the ratio in the original scale.</description>
        <time_frame>Study Day -7 to Study Day 1, or approximately 8 days</time_frame>
        <population>PK parameters were assessed in a subset of patients (N=15).</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib tablet or capsule given orally</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib tablet or capsule given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf</title>
          <description>Relative bioavailability of lucitanib was evaluated by comparison of (log-transformed) AUClast, Cmax and AUCinf of the tablet formulation to the capsule formulation using an analysis of variance (ANOVA) model with treatment as a fixed effect. The geometric means, ratio of the geometric means and 90% confidence intervals (CI) on the ratio of Tablet to Capsule (T:R) were presented for AUClast, Cmax and AUCinf. The CIs on the ratio of untransformed PK parameters were derived through reverse transformation of the 90% CI of the difference in the log scale to the 90% CI of the ratio in the original scale.</description>
          <population>PK parameters were assessed in a subset of patients (N=15).</population>
          <units>Percentage (tablet/capsule)</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cmax Geometric Mean Ratio</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.73" lower_limit="70.35" upper_limit="177.45"/>
                    <measurement group_id="O2" value="100.56" lower_limit="64.59" upper_limit="156.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUClast Geometric Mean Ratio</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97.58" lower_limit="60.61" upper_limit="157.09"/>
                    <measurement group_id="O2" value="112.2" lower_limit="78.73" upper_limit="159.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCinf Geometric Mean Ratio</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.9" lower_limit="51.75" upper_limit="132.81"/>
                    <measurement group_id="O2" value="114.23" lower_limit="70.09" upper_limit="186.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.</description>
        <time_frame>Cycle 1 Day 1 to date of death, assessed up to 29 months</time_frame>
        <population>Intent to treat population by initial treatment and overall</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O3">
            <title>All Patients</title>
            <description>The total efficacy population analyzed for response</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.</description>
          <population>Intent to treat population by initial treatment and overall</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="109"/>
                <count group_id="O2" value="69"/>
                <count group_id="O3" value="178"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.0" lower_limit="10.7" upper_limit="17.3"/>
                    <measurement group_id="O2" value="7.7" lower_limit="6.1" upper_limit="10.3"/>
                    <measurement group_id="O3" value="10.7" lower_limit="8.5" upper_limit="13.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score</title>
        <description>FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 37 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (10 items) ranging from 0 to 40; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. FACT-B Total Score is derived from adding the five subscale scores. Total possible score ranges from 0 to 148. High scale score represents a better QoL.</description>
        <time_frame>From Cycle 1 Day 1 until end of treatment, assessed up to 29 months</time_frame>
        <population>Efficacy Population defined as all patients who have received at least one dose of Lucitanib and have at least one post-baseline Investigator Overall Objective Tumor Assessment. 'Overall Number of Participants Analyzed'=participants who completed both a baseline FACT-B assessment and at least one post-baseline assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Lucitanib (CO-3810) 10 mg QD</title>
            <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O2">
            <title>Lucitanib (CO-3810) 15 mg QD</title>
            <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
          </group>
          <group group_id="O3">
            <title>All Patients</title>
            <description>The total efficacy population analyzed for response</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score</title>
          <description>FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 37 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (10 items) ranging from 0 to 40; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. FACT-B Total Score is derived from adding the five subscale scores. Total possible score ranges from 0 to 148. High scale score represents a better QoL.</description>
          <population>Efficacy Population defined as all patients who have received at least one dose of Lucitanib and have at least one post-baseline Investigator Overall Objective Tumor Assessment. 'Overall Number of Participants Analyzed'=participants who completed both a baseline FACT-B assessment and at least one post-baseline assessment.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="46"/>
                <count group_id="O3" value="126"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.422" spread="15.5134"/>
                    <measurement group_id="O2" value="-7.586" spread="17.0709"/>
                    <measurement group_id="O3" value="-4.307" spread="16.2248"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were reported from the time of first dose of lucitanib through 28 days after last dose protocol-specified treatment administration, up to approximately 30 months. In addition, study procedure-related AEs that occur after signing of the informed consent form and before administration of lucitanib were also collected.</time_frame>
      <desc>If a patient experiences the same preferred term (system organ class) multiple times, then the patient will be counted only once for that preferred term (system organ class).</desc>
      <group_list>
        <group group_id="E1">
          <title>Lucitanib (CO-3810) 10 mg QD</title>
          <description>10 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
        </group>
        <group group_id="E2">
          <title>Lucitanib (CO-3810) 15 mg QD</title>
          <description>15 mg of lucitanib daily in continuous 28-day treatment cycles until tumor progression, unacceptable toxicity, or withdrawal for other reasons</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.1)</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="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Supraventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Tooth impacted</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Atypical pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Ammonia increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </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" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Malignant pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Aphasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Renal tubular acidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Lung infiltration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.1)</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="107" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="69" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="53" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="35" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="55" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Malignant neoplasm progression</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="69"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="85" subjects_at_risk="109"/>
                <counts group_id="E2" subjects_affected="50" subjects_at_risk="69"/>
              </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>All parties agree to submit all manuscripts or abstracts to all other parties 30 days prior to submission. This will enable all parties to protect proprietary information and to provide comments based on information that may not yet be available to other parties. The sponsor may request a delay in publication if there are important intellectual property concerns relating to publication, but does not have the right to suppress publication of the study results indefinitely.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Information Department</name_or_title>
      <organization>Clovis Oncology, Inc.</organization>
      <phone>+1 415 409 7220</phone>
      <email>medinfo@clovisoncology.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02202746
org study id: CO-3810-025
nct id: NCT02202746
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether lucitanib is safe and effective in the
      treatment of patients with FGF aberrant metastatic breast cancer, as well as in the treatment
      of patients with biomarker negative (FGF non-aberrant) metastatic breast cancer.
Lucitanib is a selective, orally available tyrosine kinase inhibitor targeting FGFR1-3,
      VEGFR1-3, and PDGFRα and β, with activity in relevant cell lines and animal models.

      The first in human trial of lucitanib demonstrated that daily dosing with lucitanib can
      provide durable clinical responses in patients with FGFR1- or 11q (FGF3, FGF4, Cyclin D1, or
      FGF19)-amplified breast cancer. RECIST partial responses (PRs) were also observed in patients
      not known to have FGF abnormalities.

      Based on these results, this study is designed to explore the safety and anti-tumor activity
      of daily lucitanib in breast cancer patients with and without alterations of the FGF pathway.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator
time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
description: The primary efficacy endpoint of PFS was calculated as 1+ the number of days from the date of first dose of study drug to disease progression or death due to any cause, whichever occurs first. Patients without a documented event of progression were censored on the date of their last adequate tumor assessment (i.e., radiologic assessment), or the date of randomization if no tumor assessments were performed. Progression events were determined by the investigator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
measure: Objective Response Rate (ORR) by RECIST v1.1
time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
description: ORR is the percentage of patients with a best response of CR or PR according to RECIST v1.1. The best response is recorded from the start of the treatment (Day 1) until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
measure: Duration of Response (DR) by RECIST v1.1
time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
description: DR for complete response (CR) and partial response (PR) was measured from the date that any of these best confirmed responses was first recorded until the first date that PD was objectively documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
measure: Disease Control Rate (DCR) by RECIST v1.1
time frame: From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months
description: The DCR is defined as the percentage of patients with a best response rate of CR, PR, or SD for at least 12 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Cmax
time frame: Study Day -7 to Study Day 1, or approximately 8 days
description: The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Cmax = maximum concentration following administration of lucitanib.
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - Tmax
time frame: Study Day -7 to Study Day 1, or approximately 8 days
description: The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. Tmax = time to maximum concentration following administration of lucitanib
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUClast
time frame: Study Day -7 to Study Day 1, or approximately 8 days
description: The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUClast = area under the plasma concentration time curve from time 0 to the last quantifiable time point (24 hour)
measure: Comparative Pharmacokinetics (PK) of the Lucitanib Capsule Formulation vs. Tablet Formulation - AUCinf
time frame: Study Day -7 to Study Day 1, or approximately 8 days
description: The comparative PK study was a within-patient comparison of tablet and capsule formulations of lucitanib administered orally. PK sampling was performed at specified time points on each of the following two days: • Day -7: patients received a single administration of 10 mg or 15 mg lucitanib tablet formulation • Day 1: patients received a single administration of 10 mg or 15 mg lucitanib in capsule formulation. AUCinf = area under the plasma concentration time curve from 0 to infinity
measure: Relative Bioavailability Analysis for Tablet vs Capsule - Cmax, AUClast, AUCinf
time frame: Study Day -7 to Study Day 1, or approximately 8 days
description: Relative bioavailability of lucitanib was evaluated by comparison of (log-transformed) AUClast, Cmax and AUCinf of the tablet formulation to the capsule formulation using an analysis of variance (ANOVA) model with treatment as a fixed effect. The geometric means, ratio of the geometric means and 90% confidence intervals (CI) on the ratio of Tablet to Capsule (T:R) were presented for AUClast, Cmax and AUCinf. The CIs on the ratio of untransformed PK parameters were derived through reverse transformation of the 90% CI of the difference in the log scale to the 90% CI of the ratio in the original scale.
measure: Overall Survival
time frame: Cycle 1 Day 1 to date of death, assessed up to 29 months
description: Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Total Score
time frame: From Cycle 1 Day 1 until end of treatment, assessed up to 29 months
description: FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 37 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (10 items) ranging from 0 to 40; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. FACT-B Total Score is derived from adding the five subscale scores. Total possible score ranges from 0 to 148. High scale score represents a better QoL.
arm group label: Cohort A: Lucitanib (CO-3810) 10 mg daily
arm group type: Experimental
description: 10 mg of lucitanib daily in patients with FGFR1-amplified or 11q-amplified metastatic breast cancer.
arm group label: Cohort B: Lucitanib (CO-3810) 15 mg daily
arm group type: Experimental
description: 15 mg of lucitanib daily in patients with FGFR1-amplified and 11q-amplified metastatic breast cancer.
arm group label: Cohort C: Lucitanib (CO-3810) 10 mg daily
arm group type: Experimental
description: 10 mg of lucitanib daily in patients with FGFR1 non-amplified and 11q non-amplified metastatic breast cancer.
intervention type: Drug
intervention name: Lucitanib
description: Lucitanib is a potent, orally available selective inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors (FGFR1-3), vascular endothelial growth factor receptors (VEGFR1-3), and platelet-derived growth factor receptors alpha and beta (PDGFR alpha and beta)
arm group label: Cohort A: Lucitanib (CO-3810) 10 mg daily
arm group label: Cohort B: Lucitanib (CO-3810) 15 mg daily
arm group label: Cohort C: Lucitanib (CO-3810) 10 mg daily
other name: CO-3810
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
provided document: 
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certain agreements: 
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