<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/NCT04417192</url>
  </required_header>
  <id_info>
    <org_study_id>EPOC1903</org_study_id>
    <nct_id>NCT04417192</nct_id>
  </id_info>
  <brief_title>Olaparib Monotherapy and Olaparib + Pembrolizumab Combination Therapy for Ovarian Cancer</brief_title>
  <acronym>OLAPem</acronym>
  <official_title>A Pilot Study to Evaluate the Efficacy and Safety of Preoperative Olaparib Monotherapy and Preoperative Olaparib Plus Pembrolizumab Combination Therapy in Patients With HRD-Positive Stage III or IV Advanced Epithelial Ovarian/Fallopian Tube/Primary Peritoneal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Center Hospital East</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Center Hospital East</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>
      To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative&#xD;
      olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV&#xD;
      high-grade serous or Grade 3 endometrioid ovarian cancer with Homologous Recombination&#xD;
      Deficiency (HRD) positivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative&#xD;
      olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV&#xD;
      high-grade serous or Grade 3 endometrioid ovarian cancer with HRD positivity. The first&#xD;
      cohort (Olaparib monotherapy : 10 cases) will be evaluated for the presence or absence of&#xD;
      immune cell activation, and the tumor reduction effect will be evaluated in the second cohort&#xD;
      (Olaparib plus pembrolizumab combination therapy : 20 cases).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">June 30, 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>
    <intervention_model_description>This study has 2 cohorts. Cohort 1 is Olaparib monotherapy Cohort 2 is Olaparib plus Pembrolizumab combination therapy</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>6 weeks</time_frame>
    <description>Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence of adverse events</measure>
    <time_frame>Up to 30 days after the last dose</time_frame>
    <description>The incidences and types of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Chemotherapy response score (CRS)</measure>
    <time_frame>6 months from the end of registration</time_frame>
    <description>To evaluate the effect of histopathological treatment on patients with serous carcinoma and metastasis to the omentum. The histopathological treatment effect is determined according to the chemotherapy response score (CRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>6 months from the end of registration</time_frame>
    <description>PFS is defined as the time from the first dose to the earlier of progression assessed by the Investigator per RECIST v. 1.1 (PD) or clinical criteria, or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>6 months from the end of registration</time_frame>
    <description>OS is defined as the time from the first dose to death due to any cause.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Biomarkers</measure>
    <time_frame>2 years</time_frame>
    <description>Relationship between the germline mutation and therapeutic effect</description>
  </other_outcome>
  <other_outcome>
    <measure>The change in tumor-infiltrating lymphocytes</measure>
    <time_frame>2 years</time_frame>
    <description>Relationship between the change in tumor-infiltrating lymphocytes in tumor tissue before and after therapy, and the therapeutic effect</description>
  </other_outcome>
  <other_outcome>
    <measure>The therapeutic effect</measure>
    <time_frame>2 years</time_frame>
    <description>Relationship between the Tumor Mutation Burden (TMB) and the therapeutic effect</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Olaparib or Olaparib Plus Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1 : Olaparib will be administered for 6 weeks before surgery. Cohort 2 : Olaparib and Pembrolizumab will be administered simultaneously for 2 cycles(6 weeks) before surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Olaparib will be administered at a dose of 300mg as oral dose, twice a day.</description>
    <arm_group_label>Olaparib or Olaparib Plus Pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab will be administered at a dose of 200mg as a 30-minutes IV infusion, Q3W (25 minutes to 40 minutes are acceptable).</description>
    <arm_group_label>Olaparib or Olaparib Plus Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has given signed informed consent to participate in the clinical trial of her own&#xD;
             will.&#xD;
&#xD;
          2. Is aged 20 years or older on the day of signing the informed consent.&#xD;
&#xD;
          3. Has been diagnosed with histologically confirmed, Stage III or IV epithelial ovarian,&#xD;
             fallopian tube, or primary peritoneal cancer by the International Federation of&#xD;
             Gynecology and Obstetrics (FIGO) staging system (2014), with a histological type of&#xD;
             high-grade serous or Grade 3 endometrioid carcinoma.&#xD;
&#xD;
          4. Have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          5. Is a candidate for debulking surgery.&#xD;
&#xD;
          6. Has an HRD-positive tumor.&#xD;
&#xD;
          7. Has an ECOG Performance Status of 0 or 1.&#xD;
&#xD;
          8. Laboratory test results within 21 days prior to enrollment have met the following&#xD;
             organ function criteria. However, measurements within 14 days of blood transfusion or&#xD;
             administration of granulocyte-colony stimulating factor (G-CSF) are excluded.&#xD;
&#xD;
               -  Neutrophil count ≥ 1,500/mm3&#xD;
&#xD;
               -  Platelet count ≥ 100,000/mm3&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min&#xD;
&#xD;
               -  T-Bil ≤ 2.0 mg/dL&#xD;
&#xD;
               -  ALT and AST ≤ 100 U/L (≤ 200 U/L if liver metastasis is present)&#xD;
&#xD;
          9. A woman of childbearing potential must agree to use contraception after signing the&#xD;
             informed consent, throughout the study period, and until at least 120 days following&#xD;
             the last dose of the study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has received previous allogeneic bone-marrow transplantation.&#xD;
&#xD;
          2. Has concurrent interstitial lung disease/pneumonitis, or a history of (noninfectious)&#xD;
             interstitial lung disease/pneumonitis that required treatment with steroids.&#xD;
             Interstitial lung disease/pneumonitis includes radiation pneumonitis.&#xD;
&#xD;
          3. Has received prior antitumor therapy (e.g., chemotherapy, molecular-targeted therapy,&#xD;
             therapeutic antibody, endocrine therapy, immunotherapy, and investigational therapy).&#xD;
&#xD;
          4. Has received surgery under general anesthesia within 28 days prior to enrollment.&#xD;
             However, surgery to diagnose ovarian/fallopian tube/peritoneal cancer performed under&#xD;
             general anesthesia is allowed.&#xD;
&#xD;
          5. Has received radiation or radioactive isotope therapy within 28 days prior to&#xD;
             enrollment.&#xD;
&#xD;
          6. Has uncontrolled pericardial effusion, pleural effusion, or peritoneal effusion.&#xD;
&#xD;
          7. Has a history of cerebral infarction, cerebral hemorrhage, or transient cerebral&#xD;
             ischemia within 180 days prior to enrollment.&#xD;
&#xD;
          8. Has a history of deep vein thrombosis or pulmonary embolism.&#xD;
&#xD;
          9. Is receiving systemic glucocorticoid therapy or systemic immunosuppressive therapy.&#xD;
&#xD;
         10. Has a history of autoimmune disease.&#xD;
&#xD;
         11. Is infected with human immunodeficiency virus (HIV).&#xD;
&#xD;
         12. Is infected with active* hepatitis B or hepatitis C.&#xD;
&#xD;
             *: Active hepatitis B is defined as HBs antigen positive.&#xD;
&#xD;
         13. Has a symptomatic infection within 14 days prior to enrollment.&#xD;
&#xD;
         14. Has received a live vaccine within 28 days prior to enrollment.&#xD;
&#xD;
         15. Has clinically critical cardiac disease (has a history of myocardial infarction or&#xD;
             angina pectoris within 180 days prior to enrollment or has New York Heart Association&#xD;
             [NYHA] class II or higher cardiac failure, uncontrolled arrhythmia, or QTc&#xD;
             prolongation defined as QTc &gt; 470 msec).&#xD;
&#xD;
         16. Has active brain metastasis or a tumor causing spinal cord compression.&#xD;
&#xD;
         17. Is pregnant or breastfeeding.&#xD;
&#xD;
         18. Has a history of severe allergy, anaphylaxis, or hypersensitivity induced by humanized&#xD;
             chimeric antibodies.&#xD;
&#xD;
         19. Is allergic to biologics produced from Chinese hamster ovary (CHO) cells, carboplatin,&#xD;
             or paclitaxel.&#xD;
&#xD;
         20. Has a known or suspected active malignancy that is different from the disease of&#xD;
             interest in the clinical trial or has a history of other malignancy within 3 years&#xD;
             prior to enrollment. However, cutaneous basal cell carcinoma and cervical carcinoma in&#xD;
             situ are not part of this exclusion criterion.&#xD;
&#xD;
         21. Is unwilling to or unable to comply with the protocol.&#xD;
&#xD;
         22. Is not eligible to enroll in the clinical trial based on the judgment by the&#xD;
             Investigator or Sub-investigator.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Shikoku Cancer Center</name>
      <address>
        <city>Matsuyama</city>
        <state>Ehime</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kurume University Hospital</name>
      <address>
        <city>Kurume</city>
        <state>Fukuoka</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 4, 2023</last_update_submitted>
  <last_update_submitted_qc>July 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Center Hospital East</investigator_affiliation>
    <investigator_full_name>Toru Mukohara</investigator_full_name>
    <investigator_title>Chief of Breast and Medical Oncology Division</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Olaparib</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/NCT04417192
org study id: EPOC1903
nct id: NCT04417192
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative
      olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV
      high-grade serous or Grade 3 endometrioid ovarian cancer with Homologous Recombination
      Deficiency (HRD) positivity.
To evaluate the efficacy and safety of preoperative olaparib monotherapy and preoperative
      olaparib plus pembrolizumab combination therapy in patients with untreated stage III, IV
      high-grade serous or Grade 3 endometrioid ovarian cancer with HRD positivity. The first
      cohort (Olaparib monotherapy : 10 cases) will be evaluated for the presence or absence of
      immune cell activation, and the tumor reduction effect will be evaluated in the second cohort
      (Olaparib plus pembrolizumab combination therapy : 20 cases).
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This study has 2 cohorts. Cohort 1 is Olaparib monotherapy Cohort 2 is Olaparib plus Pembrolizumab combination therapy
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: 6 weeks
description: Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1.
measure: The incidence of adverse events
time frame: Up to 30 days after the last dose
description: The incidences and types of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
measure: Chemotherapy response score (CRS)
time frame: 6 months from the end of registration
description: To evaluate the effect of histopathological treatment on patients with serous carcinoma and metastasis to the omentum. The histopathological treatment effect is determined according to the chemotherapy response score (CRS)
measure: Progression-free survival (PFS)
time frame: 6 months from the end of registration
description: PFS is defined as the time from the first dose to the earlier of progression assessed by the Investigator per RECIST v. 1.1 (PD) or clinical criteria, or death due to any cause.
measure: Overall survival (OS)
time frame: 6 months from the end of registration
description: OS is defined as the time from the first dose to death due to any cause.
measure: Biomarkers
time frame: 2 years
description: Relationship between the germline mutation and therapeutic effect
measure: The change in tumor-infiltrating lymphocytes
time frame: 2 years
description: Relationship between the change in tumor-infiltrating lymphocytes in tumor tissue before and after therapy, and the therapeutic effect
measure: The therapeutic effect
time frame: 2 years
description: Relationship between the Tumor Mutation Burden (TMB) and the therapeutic effect
arm group label: Olaparib or Olaparib Plus Pembrolizumab
arm group type: Experimental
description: Cohort 1 : Olaparib will be administered for 6 weeks before surgery. Cohort 2 : Olaparib and Pembrolizumab will be administered simultaneously for 2 cycles(6 weeks) before surgery.
intervention type: Drug
intervention name: Olaparib
description: Olaparib will be administered at a dose of 300mg as oral dose, twice a day.
arm group label: Olaparib or Olaparib Plus Pembrolizumab
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab will be administered at a dose of 200mg as a 30-minutes IV infusion, Q3W (25 minutes to 40 minutes are acceptable).
arm group label: Olaparib or Olaparib Plus Pembrolizumab
criteria: 
gender: Female
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Japan
responsible party type: Principal Investigator
investigator affiliation: National Cancer Center Hospital East
investigator full name: Toru Mukohara
investigator title: Chief of Breast and Medical Oncology Division
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Pembrolizumab
mesh term: Olaparib