<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/NCT03249142</url>
  </required_header>
  <id_info>
    <org_study_id>GINECO-OV127b</org_study_id>
    <nct_id>NCT03249142</nct_id>
  </id_info>
  <brief_title>Immunotherapy With Neo-adjuvant Chemotherapy for OVarian Cancer</brief_title>
  <acronym>INeOV</acronym>
  <official_title>A Multicentre Feasibility Randomized Study of Anti-PD-L1 Durvalumab (MEDI4736) With or Without Anti-CTLA-4 Tremelimumab in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma, Treated With a First-line Neo-adjuvant Strategy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ARCAGY/ GINECO GROUP</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>ARCAGY/ GINECO GROUP</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, open, comparative, multi-centre study which will recruit up to 66&#xD;
      patients. The objective is mainly to explore the safety and feasibility in neo-adjuvant&#xD;
      first-line ovarian cancer (including patients with primary peritoneal or fallopian tube&#xD;
      adenocarcinoma) of various combinations of durvalumab with chemotherapy with or without&#xD;
      tremelimumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The schedule is the following:&#xD;
&#xD;
      • In a first step a run-in phase of 6 patients will be conducted to test the safety and&#xD;
      feasibility of the combination of durvalumab with standard carboplatin-paclitaxel&#xD;
      chemotherapy.&#xD;
&#xD;
      Cycle 1 : chemotherapy alone (day1) Cycle 2 : chemotherapy + durvalumab (day1) Cycle 3 :&#xD;
      chemotherapy + durvalumab (day1)&#xD;
&#xD;
      • In a second step, if first-step was found feasible, a run-in phase of 6 patients will be&#xD;
      conducted to test the safety and feasibility of the combination of durvalumab plus&#xD;
      tremelimumab with standard carboplatin-paclitaxel chemotherapy.&#xD;
&#xD;
      Cycle 1 : chemotherapy alone (day1) Cycle 2 : chemotherapy + durvalumab + tremelimumab (day1)&#xD;
      Cycle 3 : chemotherapy + durvalumab (day1)&#xD;
&#xD;
        -  After the run-in phase, patients will be randomized in a ratio 1:1 between those&#xD;
           included in the durvalumab-chemotherapy expansion phase (arm A) and those included in&#xD;
           the durvalumab + tremelimumab-chemotherapy expansion phase (arm B).&#xD;
&#xD;
        -  This study will also allow to explore the feasibility of a salvage therapy personalized&#xD;
           according to the results of interval surgery and type of previous neo-adjuvant therapy.&#xD;
&#xD;
             1. In those patients who achieved a complete surgical resection at interval debulking&#xD;
                surgery, adjuvant treatment will include 3 cycles of durvalumab + chemotherapy and&#xD;
                then a follow-up period.&#xD;
&#xD;
             2. In patients with residual tumor at interval debulking surgery, salvage therapy will&#xD;
                depend on the initial treatment arm allocated.&#xD;
&#xD;
                  1. In arm A, the tremelimumab will be added to the durvalumab-chemotherapy&#xD;
                     combination at day 1 of cycle 2 before a salvage surgery. Durvalumab (with one&#xD;
                     cycle of tremelimumab post S3) will be pursued in maintenance treatment, up to&#xD;
                     1 year or until disease progression, unacceptable toxicity or patient&#xD;
                     withdrawn.&#xD;
&#xD;
                  2. In arm B, the therapy will be according to the Investigator choice and managed&#xD;
                     according to local practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 18, 2017</start_date>
  <completion_date type="Anticipated">February 28, 2024</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2024</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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Toxicity after neo-adjuvant treatment</measure>
    <time_frame>At the end of cycle 3 (each cycle is 21 days)</time_frame>
    <description>frequency of adverse events according to CTCAE v4.03 criteria</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity after adjuvant treatment</measure>
    <time_frame>At the end of cycle 6 (each cycle is 21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity after maintenance therapy</measure>
    <time_frame>Up to 18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety after interval debulking surgery</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>adverse events according to the Clavien-Dindo classification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) based on investigator assessment using the RECIST version 1.1</measure>
    <time_frame>From date of randomisation until the date of progression or death, which ever occurs earlier, assessed up to 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sugarbaker Peritoneal Index Score (PCI)</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to start of first subsequent therapy or death</measure>
    <time_frame>Up to 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>from date of randomisation to death, assessed up to 36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">69</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>ARM A Durvalumab/chemotherapy association</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>ARM B Durvalumab/Tremelimumab/chemotherapy association</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARM A Durvalumab/chemotherapy association</intervention_name>
    <description>NEO-ADJUVANT Cycle 1 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV alone (day1), every 3 weeks Cycle 2 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1) Cycle 3 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1)&#xD;
ADJUVANT :&#xD;
If complete surgical resection at interval debulking surgery : 3 cycles of durvalumab 1125 mg IV + carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV at day1, every 3 weeks.&#xD;
If residual tumor at interval debulking surgery : the tremelimumab 75 mg IV will be added to the durvalumab-chemotherapy combination at day 1 of cycle 2 before a salvage surgery. Durvalumab 1125 mg IV (with one cycle of tremelimumab 75 mg IV post S3) will be pursued in maintenance treatment, up to 1 year or until disease progression, unacceptable toxicity or patient withdrawn.</description>
    <arm_group_label>ARM A Durvalumab/chemotherapy association</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ARM B Durvalumab/Tremelimumab/chemotherapy association</intervention_name>
    <description>NEO-ADJUVANT Cycle 1 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV alone (day1), every 3 weeks Cycle 2 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV + tremelimumab 75 mg IV (day1) Cycle 3 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1)&#xD;
ADJUVANT :&#xD;
If complete surgical resection at interval debulking surgery : 3 cycles of durvalumab 1125 mg IV + carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV at day1, every 3 weeks.&#xD;
If residual tumor at interval debulking surgery : patients will be treated according to investigator choice.</description>
    <arm_group_label>ARM B Durvalumab/Tremelimumab/chemotherapy association</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        I-1 Female patients must be ≥ 18 years of age. I-2 Signed informed consent and ability to&#xD;
        comply with treatment and follow-up. I-3 Patients with newly histologically confirmed&#xD;
        epithelial ovarian cancer (or fallopian tube or primary peritoneal adenocarcinoma).&#xD;
&#xD;
        I-4 Advanced FIGO stage IIIC to IV. I-5 Patients for whom primary debulking surgery has&#xD;
        been denied after an evaluation through laparoscopy or laparotomy.&#xD;
&#xD;
        I-6 Patient for whom a neo-adjuvant strategy has been planned. I-7 Interval between&#xD;
        diagnosis and enrolment (informed consent signed) ≤ 8 weeks.&#xD;
&#xD;
        I-8 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. I-9 Geriatric&#xD;
        vulnerability score (GVS) &lt; 3 for patients ≥ 70 years. I-10 Adequate organ and bone marrow&#xD;
        function. I-11 Patients not receiving anticoagulant medication who have an International&#xD;
        Normalized Ratio (INR) ≤ 1.5 and an Activated ProThrombin Time (aPTT) ≤ 1.5 x ULN. The use&#xD;
        of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is&#xD;
        within therapeutic limits (according to site medical standard) and if the patient is on a&#xD;
        stable dose of anticoagulants for at least two weeks at the time of randomization.&#xD;
&#xD;
        I-12 As this study will include patients in France, a subject will be eligible for&#xD;
        randomization in this study only if either affiliated to, or a beneficiary of, a social&#xD;
        category.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        E-1 Other malignancy within the last 5 years except: adequately treated non-melanoma skin&#xD;
        cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS).&#xD;
&#xD;
        E-2 Major surgical procedure (defined by the resection of at least one organ including&#xD;
        ovary) within 28 days prior to the first dose.&#xD;
&#xD;
        E-3 Any concurrent chemotherapy, investigational product, biological, or hormonal therapy&#xD;
        for cancer treatment.&#xD;
&#xD;
        E-4 Previous treatment with immunotherapy, including, but not limited to, anti-CTLA-4,&#xD;
        anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, or therapeutic anticancer vaccine.&#xD;
&#xD;
        E-5 Active or prior documented autoimmune or inflammatory disorders The following are&#xD;
        exceptions to this criterion:&#xD;
&#xD;
          1. Patients with vitiligo or alopecia,&#xD;
&#xD;
          2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone&#xD;
             replacement or psoriasis not requiring systemic treatment.&#xD;
&#xD;
        E-6 Current/prior immunosuppressive medication ≤ 14 days before first durvalumab and&#xD;
        tremelimumab dose (including, but not limited to, prednisone, dexamethasone,&#xD;
        cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor&#xD;
        [TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for&#xD;
        systemic immunosuppressive medications during the trial.&#xD;
&#xD;
        E-7 Immunocompromised patients, e.g., patients who are known to be serologically positive&#xD;
        for human immunodeficiency virus (HIV). Patients with active hepatitis B (defined as having&#xD;
        a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients&#xD;
        with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a&#xD;
        negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody&#xD;
        test) are eligible.&#xD;
&#xD;
        E-8 Uncontrolled diabetes mellitus, uncontrolled hypothyroidism. E-9 Treatment with&#xD;
        systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α)&#xD;
        and interleukin-2 (IL-2) within 4 weeks or five half- lives of the drug (whichever is&#xD;
        shorter) prior to Cycle 1, Day 1.&#xD;
&#xD;
        E-10 History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced&#xD;
        pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing&#xD;
        pneumonia), or evidence of active pneumonitis. Radiation pneumonitis in the radiation field&#xD;
        (fibrosis) detected on screening chest CT scan is permitted.&#xD;
&#xD;
        E-11 Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. E-12&#xD;
        Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or&#xD;
        anticipation that such a live attenuated vaccine will be required during the study.&#xD;
        Influenza vaccination should be given during influenza season only (example approximately&#xD;
        October to March in the Northern Hemisphere). Patients must not receive live, attenuated&#xD;
        influenza.&#xD;
&#xD;
        E-13 Current or recent (within 10 days prior to randomization) chronic use of aspirin &gt; 325&#xD;
        mg/day.&#xD;
&#xD;
        E-14 Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.&#xD;
&#xD;
        E-15 Inadequately controlled HTN (defined as systolic blood pressure &gt; 150 mmHg and/or&#xD;
        diastolic blood pressure &gt; 100 mmHg on antihypertensive medications).&#xD;
&#xD;
        E-16 Clinically significant (e.g. active) cardiovascular disease, including:&#xD;
&#xD;
          1. Myocardial infarction or unstable angina within ≤ 6 months of randomization,&#xD;
&#xD;
          2. New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF),&#xD;
&#xD;
          3. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled&#xD;
             atrial fibrillation are eligible),&#xD;
&#xD;
          4. Peripheral vascular disease grade ≥ 3 (e.g. symptomatic and interfering with&#xD;
             activities of daily living [ADL] requiring repair or revision).&#xD;
&#xD;
        E-17 Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or&#xD;
        Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.&#xD;
&#xD;
        E-18 History or evidence of hemorrhagic disorders within 6 months prior to randomization.&#xD;
&#xD;
        E-19 Evidence of bleeding diathesis or significant coagulopathy (in the absence of&#xD;
        coagulation).&#xD;
&#xD;
        E-20 History or clinical suspicion of brain metastases or spinal cord compression unless&#xD;
        asymptomatic, treated, and stable off steroids and anti-convulsants for at least 1 month&#xD;
        prior to entry.&#xD;
&#xD;
        E-21 History or evidence upon neurological examination of central nervous system (CNS)&#xD;
        disease, unless adequately treated with standard medical therapy (e.g. uncontrolled&#xD;
        seizures).&#xD;
&#xD;
        E-22 Pre-existing motor or sensory neurotoxicity (grade &gt; 1). E-23 Significant traumatic&#xD;
        injury within 4 weeks prior to randomization. E-24 Non-healing wound, active ulcer or bone&#xD;
        fracture. Patients with granulating incisions healing by secondary intention with no&#xD;
        evidence of facial dehiscence or infection are eligible but require 3 weekly wound&#xD;
        examinations.&#xD;
&#xD;
        E-25 Current, clinically relevant bowel obstruction, including sub-occlusive disease,&#xD;
        related to underlying disease.&#xD;
&#xD;
        E-26 Previous allogeneic bone marrow transplant or previous solid organ transplantation.&#xD;
&#xD;
        E-27 Patients with evidence of abdominal free air not explained by paracentesis or recent&#xD;
        surgical procedure.&#xD;
&#xD;
        E-28 Evidence of any other disease, metabolic dysfunction, physical examination finding or&#xD;
        laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
        contraindicates the use of an investigational drug or puts the patient at high risk for&#xD;
        treatment related complications.&#xD;
&#xD;
        E-29 Female patients who are pregnant or breastfeeding or male or female patients of&#xD;
        reproductive potential (&lt; 2 years after last menstruation and not surgically sterile) who&#xD;
        are not willing to employ effective birth control from screening to 180 days after the last&#xD;
        dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of&#xD;
        durvalumab monotherapy, whichever is the longer time period.&#xD;
&#xD;
        E-30 History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
        chimeric or humanized antibodies or fusion proteins.&#xD;
&#xD;
        E-31 Known hypersensitivity or allergy to biopharmaceuticals or to any component of the&#xD;
        durvalumab or tremelimumab formulations.&#xD;
&#xD;
        E-32 Known hypersensitivity reaction or allergy to drugs chemically related to carboplatin,&#xD;
        paclitaxel, or their excipients that contraindicates the subject's participation.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexandra LEARY, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Gustave Roussy, Cancer Campus, Grand Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Ste Catherine</name>
      <address>
        <city>Avignon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICM Val d'Aurelle</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe confluent</name>
      <address>
        <city>Nantes</city>
        <zip>44202</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HEGP</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Lyon Sud</name>
      <address>
        <city>Pierre-Bénite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut René Godinot</name>
      <address>
        <city>Reims</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Eugene Marquis</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie de Lorraine</name>
      <address>
        <city>Vandœuvre-lès-Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 4, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ovarian Cancer</keyword>
  <keyword>Anti-PD-L1</keyword>
  <keyword>Anti-CLA-4</keyword>
  <keyword>Neo-adjuvant</keyword>
  <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>Durvalumab</mesh_term>
    <mesh_term>Tremelimumab</mesh_term>
    <mesh_term>Antibodies, Monoclonal</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/NCT03249142
org study id: GINECO-OV127b
nct id: NCT03249142
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a randomized, open, comparative, multi-centre study which will recruit up to 66
      patients. The objective is mainly to explore the safety and feasibility in neo-adjuvant
      first-line ovarian cancer (including patients with primary peritoneal or fallopian tube
      adenocarcinoma) of various combinations of durvalumab with chemotherapy with or without
      tremelimumab.
The schedule is the following:

      • In a first step a run-in phase of 6 patients will be conducted to test the safety and
      feasibility of the combination of durvalumab with standard carboplatin-paclitaxel
      chemotherapy.

      Cycle 1 : chemotherapy alone (day1) Cycle 2 : chemotherapy + durvalumab (day1) Cycle 3 :
      chemotherapy + durvalumab (day1)

      • In a second step, if first-step was found feasible, a run-in phase of 6 patients will be
      conducted to test the safety and feasibility of the combination of durvalumab plus
      tremelimumab with standard carboplatin-paclitaxel chemotherapy.

      Cycle 1 : chemotherapy alone (day1) Cycle 2 : chemotherapy + durvalumab + tremelimumab (day1)
      Cycle 3 : chemotherapy + durvalumab (day1)

        -  After the run-in phase, patients will be randomized in a ratio 1:1 between those
           included in the durvalumab-chemotherapy expansion phase (arm A) and those included in
           the durvalumab + tremelimumab-chemotherapy expansion phase (arm B).

        -  This study will also allow to explore the feasibility of a salvage therapy personalized
           according to the results of interval surgery and type of previous neo-adjuvant therapy.

             1. In those patients who achieved a complete surgical resection at interval debulking
                surgery, adjuvant treatment will include 3 cycles of durvalumab + chemotherapy and
                then a follow-up period.

             2. In patients with residual tumor at interval debulking surgery, salvage therapy will
                depend on the initial treatment arm allocated.

                  1. In arm A, the tremelimumab will be added to the durvalumab-chemotherapy
                     combination at day 1 of cycle 2 before a salvage surgery. Durvalumab (with one
                     cycle of tremelimumab post S3) will be pursued in maintenance treatment, up to
                     1 year or until disease progression, unacceptable toxicity or patient
                     withdrawn.

                  2. In arm B, the therapy will be according to the Investigator choice and managed
                     according to local practice.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity after neo-adjuvant treatment
time frame: At the end of cycle 3 (each cycle is 21 days)
description: frequency of adverse events according to CTCAE v4.03 criteria
measure: Toxicity after adjuvant treatment
time frame: At the end of cycle 6 (each cycle is 21 days)
measure: Toxicity after maintenance therapy
time frame: Up to 18 months
measure: Safety after interval debulking surgery
time frame: Up to 6 months
description: adverse events according to the Clavien-Dindo classification
measure: Progression Free Survival (PFS) based on investigator assessment using the RECIST version 1.1
time frame: From date of randomisation until the date of progression or death, which ever occurs earlier, assessed up to 36 months
measure: Sugarbaker Peritoneal Index Score (PCI)
time frame: Up to 6 months
measure: Time to start of first subsequent therapy or death
time frame: Up to 36 months
measure: overall survival
time frame: from date of randomisation to death, assessed up to 36 months
arm group label: ARM A Durvalumab/chemotherapy association
arm group type: Experimental
arm group label: ARM B Durvalumab/Tremelimumab/chemotherapy association
arm group type: Experimental
intervention type: Drug
intervention name: ARM A Durvalumab/chemotherapy association
description: NEO-ADJUVANT Cycle 1 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV alone (day1), every 3 weeks Cycle 2 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1) Cycle 3 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1)
ADJUVANT :
If complete surgical resection at interval debulking surgery : 3 cycles of durvalumab 1125 mg IV + carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV at day1, every 3 weeks.
If residual tumor at interval debulking surgery : the tremelimumab 75 mg IV will be added to the durvalumab-chemotherapy combination at day 1 of cycle 2 before a salvage surgery. Durvalumab 1125 mg IV (with one cycle of tremelimumab 75 mg IV post S3) will be pursued in maintenance treatment, up to 1 year or until disease progression, unacceptable toxicity or patient withdrawn.
arm group label: ARM A Durvalumab/chemotherapy association
intervention type: Drug
intervention name: ARM B Durvalumab/Tremelimumab/chemotherapy association
description: NEO-ADJUVANT Cycle 1 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV alone (day1), every 3 weeks Cycle 2 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV + tremelimumab 75 mg IV (day1) Cycle 3 : carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV + durvalumab 1125 mg IV (day1)
ADJUVANT :
If complete surgical resection at interval debulking surgery : 3 cycles of durvalumab 1125 mg IV + carboplatin AUC 5 IV + paclitaxel 175 mg/m² IV at day1, every 3 weeks.
If residual tumor at interval debulking surgery : patients will be treated according to investigator choice.
arm group label: ARM B Durvalumab/Tremelimumab/chemotherapy association
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexandra LEARY, MD, PhD
role: Principal Investigator
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
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country: France
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Durvalumab
mesh term: Tremelimumab
mesh term: Antibodies, Monoclonal
sharing ipd: No