<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/NCT02978859</url>
  </required_header>
  <id_info>
    <org_study_id>AAAQ8661</org_study_id>
    <nct_id>NCT02978859</nct_id>
  </id_info>
  <brief_title>Sitravatinib in Advanced Liposarcoma and Other Soft Tissue Sarcomas</brief_title>
  <official_title>A Phase II Trial of Sitravatinib (MGCD516), a Multi-receptor Tyrosine Kinase Inhibitor, in Advanced Liposarcoma and Other Soft Tissue Sarcomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Matthew Ingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Mirati Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor&#xD;
      tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sarcomas are a group of cancers which arise from connective tissue and bone, of which more&#xD;
      than 50 subtypes exist. Approximately 12,000 people are diagnosed with sarcoma annually in&#xD;
      the United States.&#xD;
&#xD;
      Liposarcoma is one of the more common types of soft tissue sarcoma. The primary treatment for&#xD;
      liposarcoma is surgery when possible. When liposarcoma is not amenable to surgery, various&#xD;
      systemic treatments, including chemotherapy, are used. However, the effectiveness of existing&#xD;
      treatments for liposarcoma is limited.&#xD;
&#xD;
      Sitravatinib is an oral, targeted drug which inhibits receptor tyrosine kinases. Receptor&#xD;
      tyrosine kinases are proteins on the surface of the liposarcoma cell which play a role in&#xD;
      cancer growth. In laboratory work, Sitravatinib effectively suppressed the growth of&#xD;
      liposarcoma models. The purpose of this study is to evaluate the safety and efficacy of&#xD;
      Sitravatinib in patients with liposarcoma which cannot be removed by surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">January 2023</primary_completion_date>
  <phase>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>Progression free rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>To assess the efficacy of MGCD516 in patients with advanced liposarcoma by evaluating the progression free rate at 12 weeks as compared historical controls.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse event rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>To evaluate the safety profile of MGCD516.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Up to 33 months</time_frame>
    <description>To assess the efficacy of MGCD516 in patients with advanced liposarcoma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival rate</measure>
    <time_frame>Up to 33 months</time_frame>
    <description>To assess the efficacy of MGCD516 in patients with advanced liposarcoma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival rate</measure>
    <time_frame>Up to 33 months</time_frame>
    <description>To assess the efficacy of MGCD516 in patients with advanced liposarcoma.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">29</enrollment>
  <condition>Liposarcoma</condition>
  <condition>Metastatic Liposarcoma</condition>
  <arm_group>
    <arm_group_label>MGCD516</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with locally advanced and unresectable or metastatic sarcoma will receive MGCD516 at the discretion of the principal investigator until disease progression, unacceptable toxicity or adverse event(s) or withdrawal of consent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MGCD516</intervention_name>
    <description>Administered at 150 mg orally, daily, in continuous 21 day cycles. An orally available, potent small molecular inhibitor of several related receptor tyrosine kinases.</description>
    <arm_group_label>MGCD516</arm_group_label>
    <other_name>Sitravatinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stage 1, histologically confirmed well-differentiated or de-differentiated&#xD;
             liposarcoma. If stage 1 of the Simon II stage design fails to meet its endpoint for&#xD;
             liposarcoma patients, an additional 16 patients will be enrolled, composed of 4 each&#xD;
             of MPNST, synovial sarcoma, alveolar rhabdomyosarcoma and alveolar soft part sarcoma&#xD;
             (otherwise, an additional 16 patients with well-differentiated or de-differentiated&#xD;
             liposarcoma would be enrolled). Pathology review occurs at the center enrolling the&#xD;
             patient on this trial.&#xD;
&#xD;
          -  Disease must be locally advanced and unresectable or metastatic. Disease which may be&#xD;
             resected but with an associated level of morbidity deemed unacceptable by the treating&#xD;
             clinician is considered eligible.&#xD;
&#xD;
          -  Patients must have measurable disease by RECIST criteria version 1.1.&#xD;
&#xD;
          -  Patients must evidence of disease progression, either clinically or&#xD;
             radiographically,within the 8 weeks prior to study enrollment, as determined by the&#xD;
             principal investigator.&#xD;
&#xD;
          -  Patients must have been treated with at least one prior systemic regimen for sarcoma.&#xD;
             Adjuvant systemic therapy qualifies as prior therapy for the purposes of this study.&#xD;
             There is no upper limit on previous lines of therapy received. A prior line of&#xD;
             systemic therapy may include prior investigational agents received as part of other&#xD;
             clinical studies.&#xD;
&#xD;
          -  Patients must be age 18 years or older. Because no dosing or adverse event data are&#xD;
             currently available for MGCD516 in patients less than 18 years of age, children are&#xD;
             excluded from the present study, but will be eligible for future pediatric trials.&#xD;
&#xD;
          -  Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance&#xD;
             status of 0 or 1.&#xD;
&#xD;
          -  Patients must demonstrate normal organ and marrow function.&#xD;
&#xD;
          -  Patients must demonstrate adequately controlled blood pressure at the time of study&#xD;
             entry, as defined by a blood pressure ≤ 150/100 mmHg at study screening on at least&#xD;
             one of two screenings conducted at least 24 hours apart. If blood pressure meets these&#xD;
             guidelines on initial measurement, no subsequent measurement for screening is needed.&#xD;
             Blood pressure may be assessed by automated or manual methods by an appropriately&#xD;
             trained clinician or nurse.&#xD;
&#xD;
          -  Patients must have normal left ventricular systolic function, as demonstrated by a&#xD;
             transthoracic echocardiogram or multigated acquisition (MUGA) scan showing a normal&#xD;
             left ventricular ejection fraction.&#xD;
&#xD;
          -  Women of child-bearing potential and all men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) prior to study entry and for&#xD;
             the duration of study participation.&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not have received treatment with any chemotherapy, immunotherapy,&#xD;
             radiotherapy or an investigational agent for malignancy within the 28 days preceding&#xD;
             study registration. Patients may not have received treatment with nitrosureas or&#xD;
             mitomycin within the 42 days prior to study registration. Patients may not have&#xD;
             received treatment with a small molecule targeted agent (including off-label or&#xD;
             investigational use) within 14 days preceding study registration, provided this&#xD;
             represents at least 7 half-lives for that agent. Toxic effects from any prior therapy&#xD;
             (except alopecia) must have resolved to grade 1 or less according to NCI CTCAE v4.0 or&#xD;
             to the patient's baseline by the time of registration.&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agent for any purpose&#xD;
             concurrently. Patients may not require ongoing treatment with (a) gastric pH modifying&#xD;
             medications including proton pump inhibitors or H2 blockers (patients may switch to&#xD;
             antacids), (b) medications which are known to be sensitive substrates or substrates&#xD;
             with a narrow therapeutic index for the P-gp and breast cancer resistance protein&#xD;
             (BCRP) transporters and/or (c) medications known to cause corrected QT Interval (QTc)&#xD;
             prolongation with risk of Torasades. Please see Appendix 1 for a list of such&#xD;
             prohibited concomitant medications at study entry.&#xD;
&#xD;
          -  Patients with brain metastases which are symptomatic may not be enrolled. Those&#xD;
             subjects with untreated brain metastases ≤ 1 cm may who are asymptomatic and for whom&#xD;
             there are no plans for surgery, radiation or corticosteroid use may be considered&#xD;
             eligible at the discretion of the principal investigator. Subjects with brain&#xD;
             metastases that have been treated and are stable for at least 1 month are eligible if&#xD;
             they are asymptomatic and not receiving corticosteroids.&#xD;
&#xD;
          -  Patients may not have a history of allergic reaction or hypersensitivity to&#xD;
             microcrystalline cellulose (Avicel PH302) or polysorbate 80 (Tween 80), which are&#xD;
             components of the drug product MGCD516.&#xD;
&#xD;
          -  Patients may not have uncontrolled intercurrent illness including, but not limited to,&#xD;
             ongoing or active infection, symptomatic congestive heart failure, unstable angina&#xD;
             pectoris, uncontrolled cardiac arrhythmia, uncontrolled diabetes mellitus or&#xD;
             uncontrolled psychiatric illness that would limit compliance with study requirements&#xD;
             in the opinion of the principal investigator. Additionally, patients must be free of&#xD;
             any impairment in the ability to swallow and absorb the oral study drug.&#xD;
&#xD;
          -  Patients may not be pregnant or nursing. Pregnant women are excluded from this study&#xD;
             because the teratogenic effects of MGCD516 have not been adequately studied. A&#xD;
             negative pregnancy test must be documented 7 days or less prior to registration.&#xD;
             Because there is an unknown but potential risk for adverse events to nursing infants&#xD;
             secondary to treatment of the mother with MGCD516, breastfeeding must be discontinued&#xD;
             prior to registration for this clinical trial.&#xD;
&#xD;
          -  Patients may not have known HIV infection. HIV-positive patients on combination.&#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>Matthew Ingham, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachussetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114-2696</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Irving Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>November 23, 2022</last_update_submitted>
  <last_update_submitted_qc>November 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Matthew Ingham</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine; Division of Hematology and Oncology; Department of Medicine</investigator_title>
  </responsible_party>
  <keyword>MGCD516</keyword>
  <keyword>Sarcoma</keyword>
  <keyword>Liposarcoma</keyword>
  <keyword>Unresectable Liposarcoma</keyword>
  <keyword>Metastatic Liposarcoma</keyword>
  <keyword>Sitravatinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Liposarcoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02978859
org study id: AAAQ8661
nct id: NCT02978859
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate Sitravatinib, an oral small molecular receptor
      tyrosine kinase inhibitor, for the treatment of advanced liposarcoma.
Sarcomas are a group of cancers which arise from connective tissue and bone, of which more
      than 50 subtypes exist. Approximately 12,000 people are diagnosed with sarcoma annually in
      the United States.

      Liposarcoma is one of the more common types of soft tissue sarcoma. The primary treatment for
      liposarcoma is surgery when possible. When liposarcoma is not amenable to surgery, various
      systemic treatments, including chemotherapy, are used. However, the effectiveness of existing
      treatments for liposarcoma is limited.

      Sitravatinib is an oral, targeted drug which inhibits receptor tyrosine kinases. Receptor
      tyrosine kinases are proteins on the surface of the liposarcoma cell which play a role in
      cancer growth. In laboratory work, Sitravatinib effectively suppressed the growth of
      liposarcoma models. The purpose of this study is to evaluate the safety and efficacy of
      Sitravatinib in patients with liposarcoma which cannot be removed by surgery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free rate
time frame: 12 weeks
description: To assess the efficacy of MGCD516 in patients with advanced liposarcoma by evaluating the progression free rate at 12 weeks as compared historical controls.
measure: Adverse event rate
time frame: 12 weeks
description: To evaluate the safety profile of MGCD516.
measure: Overall response rate
time frame: Up to 33 months
description: To assess the efficacy of MGCD516 in patients with advanced liposarcoma.
measure: Progression free survival rate
time frame: Up to 33 months
description: To assess the efficacy of MGCD516 in patients with advanced liposarcoma.
measure: Overall survival rate
time frame: Up to 33 months
description: To assess the efficacy of MGCD516 in patients with advanced liposarcoma.
arm group label: MGCD516
arm group type: Experimental
description: Patients with locally advanced and unresectable or metastatic sarcoma will receive MGCD516 at the discretion of the principal investigator until disease progression, unacceptable toxicity or adverse event(s) or withdrawal of consent.
intervention type: Drug
intervention name: MGCD516
description: Administered at 150 mg orally, daily, in continuous 21 day cycles. An orally available, potent small molecular inhibitor of several related receptor tyrosine kinases.
arm group label: MGCD516
other name: Sitravatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Matthew Ingham, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Columbia University
investigator full name: Matthew Ingham
investigator title: Assistant Professor of Medicine; Division of Hematology and Oncology; Department of Medicine
mesh term: Sarcoma
mesh term: Liposarcoma
sharing ipd: Undecided