<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/NCT02257541</url>
  </required_header>
  <id_info>
    <org_study_id>14-140</org_study_id>
    <nct_id>NCT02257541</nct_id>
  </id_info>
  <brief_title>BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)</brief_title>
  <official_title>A Phase Ib/II Study of BGJ398 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <brief_summary>
    <textblock>
      The goal of a phase Ib clinical trial is to find the doses of drugs that are safe. Although&#xD;
      BGJ398 has been given to patients safely on its own, it has never been given together with&#xD;
      imatinib mesylate. In this study, we will test the safety of taking BGJ398 with imatinib&#xD;
      mesylate. The investigators will learn this by closely checking for side effects that the&#xD;
      patient may experience. Side effects can be seen in laboratory studies, on physical&#xD;
      examination, or by asking the patient.Once a dose has been determined to be safe, a larger&#xD;
      Phase II study will be done in patients with advanced GIST who have never received any prior&#xD;
      treatments.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2, 2014</start_date>
  <completion_date type="Actual">March 25, 2019</completion_date>
  <primary_completion_date type="Actual">March 25, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase Ib Study: Number of Participants With Dose-Limiting Toxicities</measure>
    <time_frame>1 year</time_frame>
    <description>The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Phase Ib Portion: Response Rate (RR)</measure>
    <time_frame>32 weeks</time_frame>
    <description>(CR+PR, RECIST 1.1) and by CHOI criteria&#xD;
PHASE 1b PARTICIPANTS ONLY&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Phase Ib Study: Response Rate (RR)</measure>
    <time_frame>32 weeks</time_frame>
    <description>defined by RECIST 1.1 criteria and by CHOI criteria,and by EORTC criteria&#xD;
PHASE 1b PARTICIPANTS ONLY&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Advanced Gastrointestinal Stromal Tumor (GIST)</condition>
  <arm_group>
    <arm_group_label>BGJ398 With Imatinib Mesylate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BGJ398 With Imatinib Mesylate In the phase Ib portion of the study, patients will receive imatinib at 400 mg once daily and BGJ398 at the standard 3+3 escalation doses for 21 days on, 7 days off (treatment schedule A).Using treatment schedule A, if dose level 1 to -2 is identified as the MTD and concern exists regarding therapeutic activity of BGJ398 at this dose level, expansions with higher dose levels (1 to 3) may be considered at the MSKCC PI's discretion, with modification of the treatment schedule. In this setting BGJ398 will be administered daily for one week followed by 3 weeks off and imatinib will be taken daily throughout the 4 week cycle period (treatment schedule B). In the phase II portion of the study, patients will receive imatinib at 400 mg once daily (standard of care first line imatinib dose) and BGJ398 at the RP2D and treatment schedule identified in the phase Ib portion of the study. One cycle is 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BGJ398</intervention_name>
    <arm_group_label>BGJ398 With Imatinib Mesylate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Imatinib Mesylate</intervention_name>
    <arm_group_label>BGJ398 With Imatinib Mesylate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have pathologically confirmed GIST.&#xD;
&#xD;
          -  In the Phase Ib portion, must have locally advanced or metastatic GIST and have&#xD;
             progressed on imatinib.&#xD;
&#xD;
          -  In the Phase II portion, patients must be newly diagnosed or imatinib treatment naïve&#xD;
             in the advanced/metastatic setting. Prior adjuvant imatinib therapy is allowed as long&#xD;
             as disease recurrence was documented ≥90 days after last dose of imatinib and imatinib&#xD;
             has not yet been restarted.&#xD;
&#xD;
          -  Patients must be at least 18 years of age.&#xD;
&#xD;
          -  Disease must be measurable by RECIST 1.1.&#xD;
&#xD;
          -  ECOG Performance Status 0 or 1. Adequate renal, hepatic, and hematologic function as&#xD;
             the following: Serum Creatinine ≤ 1.5 mg/dL, Total Serum Bilirubin ≤ 1.5 x upper limit&#xD;
             of normal (ULN) unless due to Gilbert's Disease, Serum AST (SGOT) and/or ALT (SGPT) ≤&#xD;
             2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor), ANC ≥ 1500/mm3, Platelets ≥&#xD;
             100,000/mm3, and hemoglobin ≥ 10g/dL.&#xD;
&#xD;
          -  Patients of childbearing potential must have a negative blood pregnancy test within 14&#xD;
             days of treatment. Patients must agree to use a reliable barrier method of birth&#xD;
             control during and for 3 months following the last dose of study drug.&#xD;
&#xD;
          -  Patient must have adequate cardiac function (left ventricular ejection fraction (LVEF)&#xD;
             ≥50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; and QTc&#xD;
             interval ≤480 ms by Fridericia's formula (QTcF).&#xD;
&#xD;
          -  Patient must be able to take oral medications.&#xD;
&#xD;
          -  Patients must sign an informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For phase I, prior intolerance to imatinib at a dose of 400 mg daily.&#xD;
&#xD;
          -  For phase II, any receipt of cytotoxic, biologic, or immune therapy aimed to treat&#xD;
             GIST except for adjuvant imatinib systemic therapy that concluded at least 90 days&#xD;
             prior to registration. For Phase I, patients are eligible regardless of prior therapy.&#xD;
&#xD;
          -  Chronic liver disease (e.g., cirrhosis)&#xD;
&#xD;
          -  Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C&#xD;
             infection.&#xD;
&#xD;
          -  Patients have a history or current evidence of Central Serous Retinopathy (CSR) or&#xD;
             retinal vein occlusion (RVO) or major predisposing factors to CSR or RVO (e.g.&#xD;
             uncontrolled glaucoma or ocular hypertension) in the opinion of the study&#xD;
             ophthalmologist.&#xD;
&#xD;
          -  History of retinal degenerative disease&#xD;
&#xD;
          -  Active corneal disorder or keratopathy (e.g. corneal abrasion, bullous keratopathy)&#xD;
&#xD;
          -  Severe and/or uncontrolled medical disease, including:&#xD;
&#xD;
               -  Uncontrolled diabetes mellitus (A1c &gt;8)&#xD;
&#xD;
               -  Chronic Kidney Disease Stage III or higher (Creatinine Clearance &lt;60mL/min/m2 by&#xD;
                  Modified Diet in Renal Disease (MDRD) calculation)&#xD;
&#xD;
               -  Active, uncontrolled infection Known active brain metastasis unless they have&#xD;
                  been treated and shown documented radiographic stability for 28 days.&#xD;
&#xD;
          -  Known other active malignancy (other than malignancies which the investigator&#xD;
             determines are unlikely to interfere with treatment and safety analysis).&#xD;
&#xD;
          -  Patients have clinically significant cardiovascular disease, including any of the&#xD;
             following&#xD;
&#xD;
               -  Any history of acute coronary syndrome including myocardial infarction, stable or&#xD;
                  unstable angina, CABG, coronary angioplasty or stenting or known obstructive&#xD;
                  coronary artery disease.&#xD;
&#xD;
               -  Symptomatic chronic heart failure (New York Heart Association Criteria, Class&#xD;
                  II-IV)&#xD;
&#xD;
               -  Evidence of clinically significant cardiac arrhythmias and/or conduction&#xD;
                  abnormalities &lt; 6 months prior to screening except atrial fibrillation (AF) and&#xD;
                  paroxysmal supraventricular tachycardia (PSVT)&#xD;
&#xD;
          -  Any history of thrombotic cerebrovascular accident or other arterial thrombosis&#xD;
&#xD;
          -  Uncontrolled arterial hypertension (systolic blood pressure &gt;155 mmHg or diastolic &gt;95&#xD;
             mmHg) despite appropriate medical therapy.&#xD;
&#xD;
          -  History and/or current evidence of uncontrolled endocrine alterations of&#xD;
             calcium/phosphate homeostasis, e.g., parathyroid disorders, history of&#xD;
             parathyroidectomy, tumor lysis, tumoral calcinosis, etc.&#xD;
&#xD;
          -  Impairment of gastrointestinal function or gastrointestinal disease (e.g.,&#xD;
             uncontrolled ulcerative disease; uncontrolled nausea, vomiting, diarrhea; chronic&#xD;
             malabsorption syndrome).&#xD;
&#xD;
          -  Patients with major surgery within 3 weeks prior to study entry or who have not&#xD;
             recovered from side effects of such procedure.&#xD;
&#xD;
          -  Women who are pregnant or lactating.&#xD;
&#xD;
          -  Sexually active males, unless they use a condom during intercourse while taking the&#xD;
             drug and for 15 days after stopping treatment. They should not father a child in this&#xD;
             period. A condom is required to be used also by vasectomized men in order to prevent&#xD;
             delivery of the drug via seminal fluid.&#xD;
&#xD;
          -  Patients with any significant history of non-adherence to medical regimens or with&#xD;
             inability to grant reliable informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William Tap, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <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>Memoral Sloan Kettering Cancer Center</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center @ Suffolk</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</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>Memorial Sloan Kettering at Mercy Medical Center</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Md Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <results_first_submitted>February 13, 2020</results_first_submitted>
  <results_first_submitted_qc>March 16, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 30, 2020</results_first_posted>
  <last_update_submitted>March 16, 2020</last_update_submitted>
  <last_update_submitted_qc>March 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BGJ398</keyword>
  <keyword>Imatinib Mesylate</keyword>
  <keyword>14-140</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Stromal Tumors</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imatinib Mesylate</mesh_term>
    <mesh_term>Infigratinib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 24, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/41/NCT02257541/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Phase 1b, Dose Level -1</title>
          <description>Phase 1b, Dose Level -1: BGJ398 50 mg</description>
        </group>
        <group group_id="P2">
          <title>Phase 1b, Dose Level 1</title>
          <description>Phase 1b, Dose Level 1: BGJ398 75 mg</description>
        </group>
        <group group_id="P3">
          <title>Phase 1b, Dose Level 2</title>
          <description>Phase 1b, Dose Level 2: BGJ398 100 mg</description>
        </group>
        <group group_id="P4">
          <title>Phase 1b, Dose Level -2</title>
          <description>Phase 1b, Dose Level -2: BGJ398 25 mg</description>
        </group>
        <group group_id="P5">
          <title>Phase II</title>
          <description>Phase II: BGJ398 75mg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Phase 1b, Dose Level -1</title>
          <description>Phase 1b, Dose Level -1: BGJ398 50 mg</description>
        </group>
        <group group_id="B2">
          <title>Phase 1b, Dose Level 1</title>
          <description>Phase 1b, Dose Level 1: BGJ398 75 mg</description>
        </group>
        <group group_id="B3">
          <title>Phase 1b, Dose Level 2</title>
          <description>Phase 1b, Dose Level 2: BGJ398 100 mg</description>
        </group>
        <group group_id="B4">
          <title>Phase 1b, Dose Level -2</title>
          <description>Phase 1b, Dose Level -2: BGJ398 25 mg</description>
        </group>
        <group group_id="B5">
          <title>Phase II</title>
          <description>Phase II: BGJ398 75mg</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="1"/>
            <count group_id="B6" value="16"/>
          </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="54" lower_limit="48" upper_limit="65"/>
                    <measurement group_id="B2" value="58.88" lower_limit="47" upper_limit="77"/>
                    <measurement group_id="B3" value="44" lower_limit="44" upper_limit="44"/>
                    <measurement group_id="B4" value="53" lower_limit="49" upper_limit="64"/>
                    <measurement group_id="B5" value="53" lower_limit="53" upper_limit="53"/>
                    <measurement group_id="B6" value="54" lower_limit="44" upper_limit="77"/>
                  </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="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase Ib Study: Number of Participants With Dose-Limiting Toxicities</title>
        <description>The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1b, Dose Level -1</title>
            <description>Phase 1b, Dose Level -1: BGJ398 50 mg</description>
          </group>
          <group group_id="O2">
            <title>Phase 1b, Dose Level 1</title>
            <description>Phase 1b, Dose Level 1: BGJ398 75 mg</description>
          </group>
          <group group_id="O3">
            <title>Phase 1b, Dose Level 2</title>
            <description>Phase 1b, Dose Level 2: BGJ398 100 mg</description>
          </group>
          <group group_id="O4">
            <title>Phase 1b, Dose Level -2</title>
            <description>Phase 1b, Dose Level -2: BGJ398 25 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Phase Ib Study: Number of Participants With Dose-Limiting Toxicities</title>
          <description>The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Phase Ib Portion: Response Rate (RR)</title>
        <description>(CR+PR, RECIST 1.1) and by CHOI criteria&#xD;
PHASE 1b PARTICIPANTS ONLY&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>32 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1b, Dose Level -1</title>
            <description>Phase 1b, Dose Level -1: BGJ398 50 mg</description>
          </group>
          <group group_id="O2">
            <title>Phase 1b, Dose Level 1</title>
            <description>Phase 1b, Dose Level 1: BGJ398 75 mg</description>
          </group>
          <group group_id="O3">
            <title>Phase 1b, Dose Level 2</title>
            <description>Phase 1b, Dose Level 2: BGJ398 100 mg</description>
          </group>
          <group group_id="O4">
            <title>Phase 1b, Dose Level -2</title>
            <description>Phase 1b, Dose Level -2: BGJ398 25 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Phase Ib Portion: Response Rate (RR)</title>
          <description>(CR+PR, RECIST 1.1) and by CHOI criteria&#xD;
PHASE 1b PARTICIPANTS ONLY&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Partial Response/PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease/SD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease/PD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not reported due to withdrawn from study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Phase Ib Study: Response Rate (RR)</title>
        <description>defined by RECIST 1.1 criteria and by CHOI criteria,and by EORTC criteria&#xD;
PHASE 1b PARTICIPANTS ONLY&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
        <time_frame>32 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Phase 1b, Dose Level -1</title>
            <description>Phase 1b, Dose Level -1: BGJ398 50 mg</description>
          </group>
          <group group_id="O2">
            <title>Phase 1b, Dose Level 1</title>
            <description>Phase 1b, Dose Level 1: BGJ398 75 mg</description>
          </group>
          <group group_id="O3">
            <title>Phase 1b, Dose Level 2</title>
            <description>Phase 1b, Dose Level 2: BGJ398 100 mg</description>
          </group>
          <group group_id="O4">
            <title>Phase 1b, Dose Level -2</title>
            <description>Phase 1b, Dose Level -2: BGJ398 25 mg</description>
          </group>
        </group_list>
        <measure>
          <title>Phase Ib Study: Response Rate (RR)</title>
          <description>defined by RECIST 1.1 criteria and by CHOI criteria,and by EORTC criteria&#xD;
PHASE 1b PARTICIPANTS ONLY&#xD;
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Progressive Disease/PD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease/SD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not reported due to withdrawn from study</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Phase 1b, Dose Level -1</title>
          <description>Phase 1b, Dose Level -1: BGJ398 50 mg</description>
        </group>
        <group group_id="E2">
          <title>Phase 1b, Dose Level 1</title>
          <description>Phase 1b, Dose Level 1: BGJ398 75 mg</description>
        </group>
        <group group_id="E3">
          <title>Phase 1b, Dose Level 2:</title>
          <description>Phase 1b, Dose Level 2: BGJ398 100 mg</description>
        </group>
        <group group_id="E4">
          <title>Phase 1b, Dose Level -2</title>
          <description>Phase 1b, Dose Level -2: BGJ398 25 mg</description>
        </group>
        <group group_id="E5">
          <title>Phase II</title>
          <description>Phase II: BGJ398 75mg</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Myocardial Infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Intra-Abdominal Bleeding</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ejection Fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lipase Increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain - Cardiac</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Flashing Lights</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Periorbital edema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Watering eyes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>AST Elevated</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>CPK Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Decreased TSH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT corrected interval prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Lipase Increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperphosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Memory Impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep Apnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry Skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. William Tap, MD</name_or_title>
      <organization>Memorial Sloan Kettering Cancer Center</organization>
      <phone>646-888-4163</phone>
      <email>tapw@mskcc.org</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/NCT02257541
org study id: 14-140
nct id: NCT02257541
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
The goal of a phase Ib clinical trial is to find the doses of drugs that are safe. Although
      BGJ398 has been given to patients safely on its own, it has never been given together with
      imatinib mesylate. In this study, we will test the safety of taking BGJ398 with imatinib
      mesylate. The investigators will learn this by closely checking for side effects that the
      patient may experience. Side effects can be seen in laboratory studies, on physical
      examination, or by asking the patient.Once a dose has been determined to be safe, a larger
      Phase II study will be done in patients with advanced GIST who have never received any prior
      treatments.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase Ib Study: Number of Participants With Dose-Limiting Toxicities
time frame: 1 year
description: The phase Ib will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.
measure: Phase Ib Portion: Response Rate (RR)
time frame: 32 weeks
description: (CR+PR, RECIST 1.1) and by CHOI criteria
PHASE 1b PARTICIPANTS ONLY
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
measure: Phase Ib Study: Response Rate (RR)
time frame: 32 weeks
description: defined by RECIST 1.1 criteria and by CHOI criteria,and by EORTC criteria
PHASE 1b PARTICIPANTS ONLY
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
arm group label: BGJ398 With Imatinib Mesylate
arm group type: Experimental
description: BGJ398 With Imatinib Mesylate In the phase Ib portion of the study, patients will receive imatinib at 400 mg once daily and BGJ398 at the standard 3+3 escalation doses for 21 days on, 7 days off (treatment schedule A).Using treatment schedule A, if dose level 1 to -2 is identified as the MTD and concern exists regarding therapeutic activity of BGJ398 at this dose level, expansions with higher dose levels (1 to 3) may be considered at the MSKCC PI's discretion, with modification of the treatment schedule. In this setting BGJ398 will be administered daily for one week followed by 3 weeks off and imatinib will be taken daily throughout the 4 week cycle period (treatment schedule B). In the phase II portion of the study, patients will receive imatinib at 400 mg once daily (standard of care first line imatinib dose) and BGJ398 at the RP2D and treatment schedule identified in the phase Ib portion of the study. One cycle is 28 days.
intervention type: Drug
intervention name: BGJ398
arm group label: BGJ398 With Imatinib Mesylate
intervention type: Drug
intervention name: Imatinib Mesylate
arm group label: BGJ398 With Imatinib Mesylate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: William Tap, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Gastrointestinal Stromal Tumors
mesh term: Imatinib Mesylate
mesh term: Infigratinib
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 