<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/NCT02219711</url>
  </required_header>
  <id_info>
    <org_study_id>516-001</org_study_id>
    <nct_id>NCT02219711</nct_id>
  </id_info>
  <brief_title>Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer</brief_title>
  <official_title>A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mirati Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mirati Therapeutics Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit&#xD;
      a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR,&#xD;
      DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with&#xD;
      advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism,&#xD;
      pharmacodynamic and clinical activity profiles.&#xD;
&#xD;
      During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the&#xD;
      Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient&#xD;
      populations.&#xD;
&#xD;
      Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor&#xD;
      type, including but not limited to, non small cell lung cancer and head and neck cancer&#xD;
      positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR&#xD;
      gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3&#xD;
      gene loci, or having loss of function mutations in the CBL gene. In addition patients with&#xD;
      clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate&#xD;
      cancer with bone metastasis will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.&#xD;
&#xD;
      During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected&#xD;
      patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based&#xD;
      upon the following cancer diagnosis:&#xD;
&#xD;
      Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA,&#xD;
      KIT or CBL.&#xD;
&#xD;
      Head and neck squamous cell carcinoma with genetic alterations in MET.&#xD;
&#xD;
      Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.&#xD;
&#xD;
      Metastatic prostate cancer with bone metastases.&#xD;
&#xD;
      Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">April 27, 2022</completion_date>
  <primary_completion_date type="Actual">April 27, 2022</primary_completion_date>
  <phase>Phase 1</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>Type of dose limiting adverse event</measure>
    <time_frame>Up to 3 weeks on treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of MGCD516</measure>
    <time_frame>Up to 72 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak Plasma Concentration (Cmax) of MGCD516</measure>
    <time_frame>Up to 72 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kind of metabolites of MGCD516 in blood plasma</measure>
    <time_frame>Up to 9 weeks on treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of selected marker proteins in blood plasma</measure>
    <time_frame>Up to 9 weeks on treatment</time_frame>
    <description>Proteins include VEGF A, soluble VEGF-R2 and soluble MET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of patients having objective disease response to treatment</measure>
    <time_frame>Up to 1 year on treatment</time_frame>
    <description>Response Evaluation Criteria in Solid Tumors (RECIST 1.1)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">193</enrollment>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>MGCD516</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MGCD516</intervention_name>
    <description>MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.</description>
    <arm_group_label>MGCD516</arm_group_label>
    <other_name>Sitravatinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic or unresectable solid tumor malignancy&#xD;
&#xD;
          -  Standard treatment is not available&#xD;
&#xD;
          -  Adequate bone marrow and organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of a significant cardiovascular illness&#xD;
&#xD;
          -  Prolonged corrected QT (QTc) interval&#xD;
&#xD;
          -  Left ventricular ejection fraction &lt; 40%&#xD;
&#xD;
          -  Symptomatic or uncontrolled brain metastases&#xD;
&#xD;
          -  Other active cancer&#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>Richard Chao, MD</last_name>
    <role>Study Director</role>
    <affiliation>Mirati Therapeutics Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</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>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarcoma Oncology Research Center</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Michael &amp; Dianne Bienes Comprehensive Cancer Center</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Affiliates</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34471</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Clinic Foundation</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology,</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University Center for Advanced Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHI Health St Francis, Saint Francis Cancer Treatment Center</name>
      <address>
        <city>Grand Island</city>
        <state>Nebraska</state>
        <zip>68803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology West PC, Nebraska Cancer Specialists</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Research and Treatment Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology Care, Inc.</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guthrie Clinical Research</name>
      <address>
        <city>Sayre</city>
        <state>Pennsylvania</state>
        <zip>18840</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Francis Cancer Center</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Austin Midtown</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75251</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas, MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology and Hematology Associates of Southwest Virginia, Inc., Blue Ridge Cancer Care</name>
      <address>
        <city>Roanoke</city>
        <state>Virginia</state>
        <zip>24014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists, P.C.</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chungbuk National University Hospital</name>
      <address>
        <city>Cheongju-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keimyung University Dongsan Hospital</name>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang-si</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea Veterans Health Service</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MGCD516</keyword>
  <keyword>MET</keyword>
  <keyword>AXL</keyword>
  <keyword>RET</keyword>
  <keyword>TRK</keyword>
  <keyword>NTRK</keyword>
  <keyword>DDR2</keyword>
  <keyword>KDR</keyword>
  <keyword>VEGFR</keyword>
  <keyword>PDGFRA</keyword>
  <keyword>KIT</keyword>
  <keyword>Tyrosine kinase inhibitor</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Non-small cell lung cancer</keyword>
  <keyword>Head and neck cancer</keyword>
  <keyword>Renal cell carcinoma</keyword>
  <keyword>Prostate cancer</keyword>
  <keyword>Phase 1</keyword>
  <keyword>CBL</keyword>
  <keyword>Sitravatinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02219711
org study id: 516-001
nct id: NCT02219711
lead sponsor: 
has dmc: No
MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit
      a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR,
      DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with
      advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism,
      pharmacodynamic and clinical activity profiles.

      During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the
      Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient
      populations.

      Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor
      type, including but not limited to, non small cell lung cancer and head and neck cancer
      positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR
      gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3
      gene loci, or having loss of function mutations in the CBL gene. In addition patients with
      clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate
      cancer with bone metastasis will be enrolled.
During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed.

      During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected
      patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based
      upon the following cancer diagnosis:

      Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA,
      KIT or CBL.

      Head and neck squamous cell carcinoma with genetic alterations in MET.

      Clear cell renal cell carcinoma refractory to angiogenesis inhibitors.

      Metastatic prostate cancer with bone metastases.

      Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Type of dose limiting adverse event
time frame: Up to 3 weeks on treatment
measure: Area under the plasma concentration versus time curve (AUC) of MGCD516
time frame: Up to 72 hours
measure: Peak Plasma Concentration (Cmax) of MGCD516
time frame: Up to 72 hours
measure: Kind of metabolites of MGCD516 in blood plasma
time frame: Up to 9 weeks on treatment
measure: Concentration of selected marker proteins in blood plasma
time frame: Up to 9 weeks on treatment
description: Proteins include VEGF A, soluble VEGF-R2 and soluble MET
measure: Percent of patients having objective disease response to treatment
time frame: Up to 1 year on treatment
description: Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
arm group label: MGCD516
arm group type: Experimental
description: MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles
intervention type: Drug
intervention name: MGCD516
description: MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.
arm group label: MGCD516
other name: Sitravatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Chao, MD
role: Study Director
affiliation: Mirati Therapeutics Inc.
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country: Korea, Republic of
country: United States
responsible party type: Sponsor
mesh term: Neoplasms