<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/NCT03798106</url>
  </required_header>
  <id_info>
    <org_study_id>4-2018-0743</org_study_id>
    <nct_id>NCT03798106</nct_id>
  </id_info>
  <brief_title>A Study of Pazopanib and Durvalumab for Metastatic Soft Tissue Sarcoma</brief_title>
  <official_title>A Phase II Trial of Pazopanib and Durvalumab for Metastatic Soft Tissue Sarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pazopanib is an angiogenesis inhibitor targeting VEGFR-1, -2, and -3; PDGFR-α and -β; and the&#xD;
      receptor c-Kit, and is indicated for the treatment of subjects with advanced renal cell&#xD;
      carcinoma (RCC) and advanced STS. For this orphan tumor, STS, PD-L1 targeting may be a&#xD;
      promising strategy and favorable toxicity may warrant further combination.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pazopanib is an angiogenesis inhibitor targeting VEGFR-1, -2, and -3; PDGFR-α and -β; and the&#xD;
      receptor c-Kit, and is indicated for the treatment of subjects with advanced renal cell&#xD;
      carcinoma (RCC) and advanced STS. Pro-angiogenic factors suppress various immune functions&#xD;
      whereas antiangiogenic agents have potential to modulate the tumor microenvironment and&#xD;
      improve immunotherapy. An analysis of patients with RCC treated with pazopanib demonstrated&#xD;
      that elevated expression of PD-L1 correlates with shorter PFS. Investigator also identified&#xD;
      43% of PD-L1 expression in STS and PD-L1 expression had worse overall survival (5-year&#xD;
      survival rate: 48% in PD-L1 positive vs. 68% in PD-L1 negative, p=0.015). In detail, PD-L1&#xD;
      expression was reported 52.6% in synovial sarcoma, 37.6% in rhabdomyosarcoma, and 100% in&#xD;
      epithelioid sarcoma. For this orphan tumor, STS, PD-L1 targeting may be a promising strategy&#xD;
      and favorable toxicity may warrant further combination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 10, 2019</start_date>
  <completion_date type="Actual">August 10, 2022</completion_date>
  <primary_completion_date type="Actual">August 10, 2022</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>Objective Response Rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>antitumor efficacy of durvalumab and pazopanib</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>durvalumab+pazopanib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab 1500mg IV 1hr q3weeks Pazopanib 800mg QD PO q3wwks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab, pazopanib</intervention_name>
    <description>Durvalumab 1500mg IV 1hr q3weeks Pazopanib 800mg QD PO q3wwks</description>
    <arm_group_label>durvalumab+pazopanib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed STS progression to 1 or 2 prior chemotherapy&#xD;
&#xD;
          2. Age &gt; 18 years at time of study entry.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          4. Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1&#xD;
&#xD;
          5. Body weight &gt;30kg&#xD;
&#xD;
          6. Adequate laboratory findings&#xD;
&#xD;
          7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients.&#xD;
&#xD;
          8. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
&#xD;
          9. Must have a life expectancy of at least 12 weeks&#xD;
&#xD;
         10. Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
             protocol.&#xD;
&#xD;
         11. Patients with evidence of portal hypertension (including splenomegaly detected&#xD;
             radiographically) or any prior history of variceal bleeding must have had endoscopic&#xD;
             evaluation within the 3 months immediately prior to enrollment, and the findings do&#xD;
             not represent a high bleeding risk.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. More than 4 prior cytotoxic regimens&#xD;
&#xD;
          2. Participation in another clinical study with an investigational product during the&#xD;
             last 2 weeks&#xD;
&#xD;
          3. Receipt of the last dose of anticancer therapy 14 days prior to the first dose of&#xD;
             study drug&#xD;
&#xD;
          4. Any previous treatment with a PD1 or PD-L1 inhibitor (including durvalumab) and/or&#xD;
             pazopanib&#xD;
&#xD;
          5. Mean QT interval corrected for heart rate (QTc) &gt;480 ms calculated from 3&#xD;
             electrocardiograms (ECGs) using Fridericia's Correction&#xD;
&#xD;
          6. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the&#xD;
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion&#xD;
             criteria&#xD;
&#xD;
          7. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment within&#xD;
             2 weeks prior to entering the study. Concurrent use of hormonal therapy for&#xD;
             non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable&#xD;
&#xD;
          8. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of&#xD;
             radiation within 4 weeks of the first dose of study drug&#xD;
&#xD;
          9. Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of IP.&#xD;
&#xD;
         10. History of allogenic organ transplantation.&#xD;
&#xD;
         11. Active or prior documented autoimmune or inflammatory disorders&#xD;
&#xD;
         12. Uncontrolled intercurrent illness&#xD;
&#xD;
         13. History of active infection&#xD;
&#xD;
         14. History of another primary malignancy&#xD;
&#xD;
         15. History of leptomeningeal carcinomatosis who are neurologically unstable or have&#xD;
             required active treatment&#xD;
&#xD;
         16. Receipt of live attenuated vaccine within 30 days prior to the first dose of&#xD;
             investigational product(IP).&#xD;
&#xD;
         17. Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
             reproductive potential who are not willing to employ effective birth control from&#xD;
             screening to 90 days after the last dose.&#xD;
&#xD;
         18. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#xD;
&#xD;
         19. No history of any of the following in the past 6 months: cardiac angioplasty or&#xD;
             stenting, myocardial infarction, unstable angina, coronary artery bypass graft&#xD;
             surgery, symptomatic peripheral vascular disease class III or IV congestive heart&#xD;
             failure, as defined by the New York Heart Association), thromboembolic events&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>June 8, 2023</last_update_submitted>
  <last_update_submitted_qc>June 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yonsei University</investigator_affiliation>
    <investigator_full_name>Hyo Song Kim</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03798106
org study id: 4-2018-0743
nct id: NCT03798106
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Pazopanib is an angiogenesis inhibitor targeting VEGFR-1, -2, and -3; PDGFR-α and -β; and the
      receptor c-Kit, and is indicated for the treatment of subjects with advanced renal cell
      carcinoma (RCC) and advanced STS. For this orphan tumor, STS, PD-L1 targeting may be a
      promising strategy and favorable toxicity may warrant further combination.
Pazopanib is an angiogenesis inhibitor targeting VEGFR-1, -2, and -3; PDGFR-α and -β; and the
      receptor c-Kit, and is indicated for the treatment of subjects with advanced renal cell
      carcinoma (RCC) and advanced STS. Pro-angiogenic factors suppress various immune functions
      whereas antiangiogenic agents have potential to modulate the tumor microenvironment and
      improve immunotherapy. An analysis of patients with RCC treated with pazopanib demonstrated
      that elevated expression of PD-L1 correlates with shorter PFS. Investigator also identified
      43% of PD-L1 expression in STS and PD-L1 expression had worse overall survival (5-year
      survival rate: 48% in PD-L1 positive vs. 68% in PD-L1 negative, p=0.015). In detail, PD-L1
      expression was reported 52.6% in synovial sarcoma, 37.6% in rhabdomyosarcoma, and 100% in
      epithelioid sarcoma. For this orphan tumor, STS, PD-L1 targeting may be a promising strategy
      and favorable toxicity may warrant further combination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: 12 weeks
description: antitumor efficacy of durvalumab and pazopanib
arm group label: durvalumab+pazopanib
arm group type: Experimental
description: Durvalumab 1500mg IV 1hr q3weeks Pazopanib 800mg QD PO q3wwks
intervention type: Drug
intervention name: Durvalumab, pazopanib
description: Durvalumab 1500mg IV 1hr q3weeks Pazopanib 800mg QD PO q3wwks
arm group label: durvalumab+pazopanib
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Yonsei University
investigator full name: Hyo Song Kim
investigator title: professor
mesh term: Sarcoma
mesh term: Durvalumab
sharing ipd: No