<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/NCT03802071</url>
  </required_header>
  <id_info>
    <org_study_id>4-2018-0746</org_study_id>
    <nct_id>NCT03802071</nct_id>
  </id_info>
  <brief_title>A Study of Durvalumab in Combination With Doxorubicin for Advanced Soft Tissue Sarcoma</brief_title>
  <official_title>A Phase I/II Study of Durvalumab in Combination With Standard Chemotherapy Doxorubicin for Advanced 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>
      The yearly incidence of soft-tissue sarcomas (STS) in the USA is roughly 11,280 cases, and&#xD;
      metastatic STS have a median overall survival of about 12 months. Sarcomas of the soft tissue&#xD;
      are a heterogeneous group of malignant tumors of mesenchymal origin that originate in&#xD;
      connective tissue. Local control with wide surgical resection with or without adjuvant&#xD;
      radiation has a success rate of close to 90%. However, approximately 40% to 50% of patients&#xD;
      with a large (&gt;5 cm), deep, high-grade soft-tissue sarcoma eventually develop distant&#xD;
      metastases, primarily in the lung. Therefore, overall survival of metastatic STS remained&#xD;
      still poor, less than 1 year. Therefore, current clinical trials with various targeted agents&#xD;
      are ongoing add on the doxorubicin monotherapy.&#xD;
&#xD;
      Investigator planned to conduct the phase I/II trial of durvalumab in combination with&#xD;
      standard chemotherapy, doxorubicin for metastatic/recurred sofe tissue sarcoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The yearly incidence of soft-tissue sarcomas (STS) in the USA is roughly 11,280 cases, and&#xD;
      metastatic STS have a median overall survival of about 12 months. Sarcomas of the soft tissue&#xD;
      are a heterogeneous group of malignant tumors of mesenchymal origin that originate in&#xD;
      connective tissue. Local control with wide surgical resection with or without adjuvant&#xD;
      radiation has a success rate of close to 90%. However, approximately 40% to 50% of patients&#xD;
      with a large (&gt;5 cm), deep, high-grade soft-tissue sarcoma (STS) eventually develop distant&#xD;
      metastases, primarily in the lung. Therefore, overall survival (OS) of metastatic STS&#xD;
      remained still poor, less than 1 year. Therefore, current clinical trials with various&#xD;
      targeted agents are ongoing add on the doxorubicin monotherapy.&#xD;
&#xD;
      Durvalumab (MEDI4736) is a human monoclonal antibody that inhibits binding of PD-L1. For this&#xD;
      orphan tumor, STS, PD-L1 may be a promising strategy and favorable toxicity may warrant&#xD;
      further combination. For this orphan tumor, STS, PD-L1 targeting may be a promising strategy&#xD;
      and favorable toxicity may warrant further combination. Regarding anti-PD-L1 treatment in&#xD;
      STS, in phase I trial with human monoclonal antibody to PD-L1, MPDL3280A, one heavily treated&#xD;
      synovial sarcoma patients demonstrated partial responses. In recent phase II study of&#xD;
      pembrolizumab, PD-1 inhibitor in advanced STS among the 40 STS cases (17.5%) had responses (1&#xD;
      complete response and 6 partial response). Based on the study, pembrolizumab monotherapy was&#xD;
      approved for previously treated STS in Korea.&#xD;
&#xD;
      Therefore, various clinical trials are ongoing immune checkpoint inhibitor with PDGFR&#xD;
      inhibitors [axitinib for renal cell carcinoma (RCC), pazopanib for RCC and STS, Sorafenib for&#xD;
      RCC, and liver cancer, sunitinib for RCC, gastrointestinal stromal tumor, and pancreatic&#xD;
      cancer].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 16, 2019</start_date>
  <completion_date type="Anticipated">August 10, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 10, 2022</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>adverse event</measure>
    <time_frame>3 weeks</time_frame>
    <description>to evaluate the safety and tolerability of durvalumab in combination with doxorubicin</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Sarcoma</condition>
  <arm_group>
    <arm_group_label>Durvalumab+doxorubicin combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab+doxorubicin cobination</intervention_name>
    <description>Durvalumab 1500mg IV Doxorubicin 75mg/m2 IV D1 Q3weeks (up to 8cycles)</description>
    <arm_group_label>Durvalumab+doxorubicin combination</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed STS(soft tissue sarcoma)&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          3. Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1&#xD;
&#xD;
          4. Body weight &gt;30kg&#xD;
&#xD;
          5. Adequate normal organ and marrow function as defined below:&#xD;
&#xD;
          6. Left ventricular ejection fraction (LVEF) ≥ 45%&#xD;
&#xD;
          7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for&#xD;
             female pre-menopausal patients. Women will be considered post-menopausal if they have&#xD;
             been amenorrheic for 12 months without an alternative medical cause.&#xD;
&#xD;
          8. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#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. Written informed consent and any locally required authorization obtained&#xD;
             from the patient/legal representative prior to performing any protocol-related&#xD;
             procedures, including screening evaluations&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histologically- or cytologically-confirmed Kaposi's sarcoma or GIST&#xD;
&#xD;
          2. Previous treatment with anthracyclines&#xD;
&#xD;
          3. Participation in another clinical study with an investigational product during the&#xD;
             last 2 weeks&#xD;
&#xD;
          4. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine&#xD;
             therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal&#xD;
             antibodies, other investigational agent) 14 days prior to the first dose of study drug&#xD;
&#xD;
          5. Any previous treatment with a PD1 or PD-L1 inhibitor (including durvalumab) and/or&#xD;
             PDGFR inhibitor&#xD;
&#xD;
          6. Mean QT interval corrected for heart rate (QTc) &gt; 480 ms calculated from 3&#xD;
             electrocardiograms (ECGs) using Fridericia's Correction&#xD;
&#xD;
          7. 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;
          8. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment within&#xD;
             14 days 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;
          9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of&#xD;
             radiation within 14 days of the first dose of study drug&#xD;
&#xD;
         10. Major surgical procedure (as defined by the Investigator) within 28 days prior to the&#xD;
             first dose of IP(investigational product).&#xD;
&#xD;
         11. History of allogenic organ transplantation.&#xD;
&#xD;
         12. Active or prior documented autoimmune or inflammatory disorders&#xD;
&#xD;
         13. Uncontrolled intercurrent illness&#xD;
&#xD;
         14. Known active infection&#xD;
&#xD;
         15. History of another primary malignancy&#xD;
&#xD;
         16. History of leptomeningeal carcinomatosis who are neurologically unstable or have&#xD;
             required active treatment&#xD;
&#xD;
         17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.&#xD;
&#xD;
         18. 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;
         19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#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>May 2022</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>May 30, 2022</last_update_submitted>
  <last_update_submitted_qc>May 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2022</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>Doxorubicin</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
  </intervention_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/NCT03802071
org study id: 4-2018-0746
nct id: NCT03802071
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The yearly incidence of soft-tissue sarcomas (STS) in the USA is roughly 11,280 cases, and
      metastatic STS have a median overall survival of about 12 months. Sarcomas of the soft tissue
      are a heterogeneous group of malignant tumors of mesenchymal origin that originate in
      connective tissue. Local control with wide surgical resection with or without adjuvant
      radiation has a success rate of close to 90%. However, approximately 40% to 50% of patients
      with a large (>5 cm), deep, high-grade soft-tissue sarcoma eventually develop distant
      metastases, primarily in the lung. Therefore, overall survival of metastatic STS remained
      still poor, less than 1 year. Therefore, current clinical trials with various targeted agents
      are ongoing add on the doxorubicin monotherapy.

      Investigator planned to conduct the phase I/II trial of durvalumab in combination with
      standard chemotherapy, doxorubicin for metastatic/recurred sofe tissue sarcoma.
The yearly incidence of soft-tissue sarcomas (STS) in the USA is roughly 11,280 cases, and
      metastatic STS have a median overall survival of about 12 months. Sarcomas of the soft tissue
      are a heterogeneous group of malignant tumors of mesenchymal origin that originate in
      connective tissue. Local control with wide surgical resection with or without adjuvant
      radiation has a success rate of close to 90%. However, approximately 40% to 50% of patients
      with a large (>5 cm), deep, high-grade soft-tissue sarcoma (STS) eventually develop distant
      metastases, primarily in the lung. Therefore, overall survival (OS) of metastatic STS
      remained still poor, less than 1 year. Therefore, current clinical trials with various
      targeted agents are ongoing add on the doxorubicin monotherapy.

      Durvalumab (MEDI4736) is a human monoclonal antibody that inhibits binding of PD-L1. For this
      orphan tumor, STS, PD-L1 may be a promising strategy and favorable toxicity may warrant
      further combination. For this orphan tumor, STS, PD-L1 targeting may be a promising strategy
      and favorable toxicity may warrant further combination. Regarding anti-PD-L1 treatment in
      STS, in phase I trial with human monoclonal antibody to PD-L1, MPDL3280A, one heavily treated
      synovial sarcoma patients demonstrated partial responses. In recent phase II study of
      pembrolizumab, PD-1 inhibitor in advanced STS among the 40 STS cases (17.5%) had responses (1
      complete response and 6 partial response). Based on the study, pembrolizumab monotherapy was
      approved for previously treated STS in Korea.

      Therefore, various clinical trials are ongoing immune checkpoint inhibitor with PDGFR
      inhibitors [axitinib for renal cell carcinoma (RCC), pazopanib for RCC and STS, Sorafenib for
      RCC, and liver cancer, sunitinib for RCC, gastrointestinal stromal tumor, and pancreatic
      cancer].
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: adverse event
time frame: 3 weeks
description: to evaluate the safety and tolerability of durvalumab in combination with doxorubicin
arm group label: Durvalumab+doxorubicin combination
arm group type: Experimental
intervention type: Drug
intervention name: Durvalumab+doxorubicin cobination
description: Durvalumab 1500mg IV Doxorubicin 75mg/m2 IV D1 Q3weeks (up to 8cycles)
arm group label: Durvalumab+doxorubicin combination
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: Doxorubicin
mesh term: Durvalumab