<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/NCT03245892</url>
  </required_header>
  <id_info>
    <org_study_id>17-182</org_study_id>
    <nct_id>NCT03245892</nct_id>
  </id_info>
  <brief_title>A Study of Carboplatin and Paclitaxel Chemotherapy With Nivolumab With or Without Ipilimumab in Patients With Ovarian Cancer</brief_title>
  <official_title>A Pilot Study of Nivolumab With or Without Ipilimumab in Combination With Front-Line Neoadjuvant Dose Dense Paclitaxel and Carboplatin Chemotherapy and Post-Surgical Dose Dense Paclitaxel and Carboplatin Chemotherapy in Patients With High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <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 find out what effects, good or bad, the addition of nivolumab&#xD;
      or the combination of nivolumab plus ipilimumab to typical chemotherapy has on the treatment&#xD;
      of advanced high-grade serous cancers of ovarian, fallopian tube, or primary peritoneal&#xD;
      origin. The typical chemotherapy treatment is Carboplatin and Paclitaxel.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 4, 2017</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Single center, non-randomized, open label, pilot study to evaluate the safety and tolerability of neoadjuvant and post-surgical dose dense paclitaxel and carboplatin chemotherapy in combination with nivolumab for the treatment of advanced high grade serous cancers of ovarian, fallopian tube, or primary peritoneal origin.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>number of patients with dose limiting toxicities with weekly paclitaxel/carboplatin plus nivolumab</measure>
    <time_frame>6 weeks</time_frame>
    <description>The safety of this regimen will be assessed by determination of the DLTs observed in the study population. If &gt;=3/10 DLTs are seen we will deem the regimen not safe and stop the trial early. If &gt;=5/20 patients have DLTs the treatment regimen would be deemed unsafe. Enrollment will be halted after 10 patients have accrued until all 10 patients have cleared the DLT period of 6 weeks</description>
  </primary_outcome>
  <primary_outcome>
    <measure>number of patients with dose limiting toxicities weekly paclitaxel/carboplatin plus nivolumab and ipilimumab</measure>
    <time_frame>6 weeks</time_frame>
    <description>The safety of this regimen will be assessed by determination of the DLTs observed in the study population. If &gt;=3/10 DLTs are seen we will deem the regimen not safe and stop the trial early. If &gt;=5/20 patients have DLTs the treatment regimen would be deemed unsafe. Enrollment will be halted after 10 patients have accrued until all 10 patients have cleared the DLT period of 6 weeks</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>High Grade Serous Ovarian</condition>
  <condition>Fallopian Tube</condition>
  <condition>Primary Peritoneal Cancer</condition>
  <arm_group>
    <arm_group_label>Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with nivolumab plus standard of care dose dense paclitaxel and carboplatin for three cycles, where each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen administered as adjuvant treatment. Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle. Carboplatin dose calculation instructions can be found in Appendix 4. Nivolumab 360mg will be infused IV over approximately 30min on Day 1 of Cycles 1-6. During the maintenance phase, Nivolumab 480mg will be infused IV on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nivolumab plus Ipilimumab plus Paclitaxel &amp; Carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be treated with nivolumab plus ipilimumab plus standard of care dose dense paclitaxel &amp; carboplatin chemotherapy for 3 cycles (up to a maximum of six), each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen. Paclitaxel 80mg/m2 IV will be administered over approx 1 hour on Days 1,8, &amp; 15 of each 21 day cycle. Carboplatin AUC6 will be administered as an approx 30 minute IV infusion, following paclitaxel admin on Day 1 of each 21 day cycle. Nivolumab 360mg will be infused IV over approx 30 min on Day 1 of Cycles 1-6 (to 9) of each 21 day cycle. Ipilimumab 1mg/kg will be infused IV over approx 30 min on Day 1 of Cycles 1 &amp; 3, as well as Cycle 4 &amp; Cycle 6. Of note, if patients receive more than 3 cycles in the pre-operative setting, then ipilimumab will be administered with the first &amp; third cycle in the post-operative setting. Nivolumab will then be infused Day 1 of each 28 day maintenance phase cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin and Paclitaxel</intervention_name>
    <description>Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle.</description>
    <arm_group_label>Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)</arm_group_label>
    <arm_group_label>Nivolumab plus Ipilimumab plus Paclitaxel &amp; Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab 360mg will be infused IV over approximately 30 min on Day 1 of Cycles 1-6 (to 8) of each 21 day cycle. During the maintenance phase, Nivolumab 480mg will be infused IV over approximately 30 min on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks</description>
    <arm_group_label>Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)</arm_group_label>
    <arm_group_label>Nivolumab plus Ipilimumab plus Paclitaxel &amp; Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cytoreductive surgery</intervention_name>
    <description>Cytoreductive surgery</description>
    <arm_group_label>Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)</arm_group_label>
    <arm_group_label>Nivolumab plus Ipilimumab plus Paclitaxel &amp; Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>Ipilimumab 1mg/kg every 6 weeks x 3-6 cycles in the neoadjuvant setting (maximum 2 doses of ipilimumab)</description>
    <arm_group_label>Nivolumab plus Ipilimumab plus Paclitaxel &amp; Carboplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have clinically and radiographically suspected International Federation&#xD;
             of Gynecology and Obstetrics (FIGO) stage (Appendix 2) 3 or 4 high grade serous&#xD;
             ovarian, primary peritoneal or fallopian tube cancer, high grade, for whom the plan of&#xD;
             management will include neoadjuvant chemotherapy (NACT) with interval tumor reductive&#xD;
             surgery (TRS). Patients will be selected for NACT according to established criteria&#xD;
             (Society of Gynecologic Oncology and the American Society of Clinical Oncology&#xD;
             Guideline, https://www.ncbi.nlm.nih.gov/pubmed/27650684). Patients must have undergone&#xD;
             core needle biopsy for histologic confirmation prior to start of treatment. See&#xD;
             Appendix 3 for guidelines to aid in histologic diagnosis.&#xD;
&#xD;
          -  Institutional confirmation of pathology on or laparoscopic biopsy performed at MSKCC&#xD;
             with sufficient tissue for analysis or willingness to undergo repeat laproscopic&#xD;
             biopsy if diagnostic biopsy was performed at an outside hospital.&#xD;
&#xD;
          -  Appropriate stage for study entry based on the following diagnostic workup:&#xD;
&#xD;
               -  History/physical examination within 28 days prior to registration;&#xD;
&#xD;
               -  CT imaging of the chest, abdomen and pelvis within 28 days prior to registration&#xD;
                  documenting disease consistent with FIGO stage III or IV disease (patients who&#xD;
                  cannot receive contrast may instead undergo MRI of abdomen and pelvis along with&#xD;
                  non-contrast chest CT);&#xD;
&#xD;
               -  Further protocol-specific assessments as detailed below.&#xD;
&#xD;
          -  Age ≥18&#xD;
&#xD;
          -  ECOG Status of 0, 1, or 2 within 28 days prior to registration.&#xD;
&#xD;
          -  Adequate hematologic function within 14 days prior to registration defined as follows:&#xD;
&#xD;
               -  ANC ≥1,000/mcl. This ANC cannot have been induced by granulocyte colony&#xD;
                  stimulating factors.&#xD;
&#xD;
               -  Platelets ≥75,000/mc&#xD;
&#xD;
               -  Hemoglobin ≥8.0 mg/dl (transfusions are permitted to achieve baseline hemoglobin&#xD;
                  level)&#xD;
&#xD;
          -  Adequate renal function within 14 days prior to registration defined as follows:&#xD;
&#xD;
             °Creatinine &lt;=1.5 x ULN.&#xD;
&#xD;
          -  Adequate hepatic function within 14 days prior to registration defined as follows:&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
               -  ALT and AST ≤ 3 x ULN&#xD;
&#xD;
               -  Alkaline phosphatase ≤ 2.5 x ULN&#xD;
&#xD;
               -  For patients with Gilbert's syndrome, Bilirubin ≤ 3 xULN is acceptable.&#xD;
&#xD;
          -  Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE Grade&#xD;
             1.&#xD;
&#xD;
          -  Adequate thyroid function within 14 days prior to registration defined as serum TSH&#xD;
             within the normal range.&#xD;
&#xD;
          -  The patient or legally authorized representative must provide study-specific informed&#xD;
             consent prior to study entry.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of other invasive malignancies, with the exception of&#xD;
             non-melanoma skin cancer, are excluded if there is any evidence of other malignancy&#xD;
             being present within the last 3 years. Subjects are also excluded if their previous&#xD;
             cancer treatment contraindicates this protocol's therapy.&#xD;
&#xD;
          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity&#xD;
             or pelvis or thoracic cavity within the last three years are excluded. Prior radiation&#xD;
             for localized cancer of the breast, head and neck or skin is permitted, provided that&#xD;
             it was completed more than three years prior to registration, and the patient remains&#xD;
             free of recurrent or metastatic disease.&#xD;
&#xD;
          -  Patients who have received any prior treatment for management of their epithelial&#xD;
             ovarian, fallopian tube or peritoneal primary cancer.&#xD;
&#xD;
          -  Patients with any histology other than high grade serous evident on pretreatment&#xD;
             biopsy.&#xD;
&#xD;
          -  Patients with synchronous primary endometrial cancer, or a past history of primary&#xD;
             endometrial cancer, unless all of the following conditions are met: Stage not greater&#xD;
             than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular&#xD;
             or lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell&#xD;
             or other FIGO grade 3 lesions.&#xD;
&#xD;
          -  Severe, active co-morbidity defined as follows:&#xD;
&#xD;
          -  Chronic or current active infectious disease requiring systemic antibiotics,&#xD;
             antifungal or antiviral treatment (with the exception of uncomplicated UTI)&#xD;
&#xD;
          -  Clinically significant cardiac disease including unstable angina, acute myocardial&#xD;
             infarction within 6 months from enrollment, New York Heart Association Class III or IV&#xD;
             congestive heart failure, and serious arrhythmia requiring medication (this does not&#xD;
             include asymptomatic atrial fibrillation with controlled ventricular rate).&#xD;
&#xD;
          -  Partial or complete gastrointestinal obstruction&#xD;
&#xD;
          -  Patients with anticipated contraindications to interval tumor reductive surgery.&#xD;
&#xD;
          -  Patients with any condition that in the judgment of the investigator would jeopardize&#xD;
             safety or patient compliance with the protocol.&#xD;
&#xD;
          -  Patients who are unwilling to be transfused with blood components.&#xD;
&#xD;
          -  Concurrent anticancer non protocol directed therapy (e.g. chemotherapy, radiation&#xD;
             therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy).&#xD;
&#xD;
          -  Receipt of an investigational study drug for any indication within 28 days or 5&#xD;
             half-lives (whichever is longer) prior to Day 1 of protocol therapy.&#xD;
&#xD;
          -  Patients who, in the opinion of the investigator, are unable or unlikely to comply&#xD;
             with the dosing schedule and study evaluations.&#xD;
&#xD;
          -  Patients who are pregnant or nursing. The effects of nivolumab on the developing human&#xD;
             fetus are unknown. For this reason, women of child-bearing potential (WOCBP) must&#xD;
             agree to use adequate contraception (hormonal or barrier method of birth control;&#xD;
             abstinence) prior to study entry and for the duration of study participation. WOCBP&#xD;
             must have a negative serum or urine pregnancy test within 7 days of study enrollment,&#xD;
             prior to dosing nivolumab, then every 6 weeks. After discontinuation from nivolumab&#xD;
             these should be repeated at approximately 30 days and approximately 70 days. Women&#xD;
             must not be breastfeeding.&#xD;
&#xD;
               1. Women who are not of childbearing potential (i.e., who are postmenopausal or&#xD;
                  surgically sterile) do not require contraception.&#xD;
&#xD;
               2. Women of childbearing potential (WOCBP) is defined as any female who has&#xD;
                  experienced menarche and who has not undergone surgical sterilization&#xD;
                  (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal.&#xD;
                  Menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the&#xD;
                  absence of other biological or physiological causes. In addition, women under the&#xD;
                  age of 55 must have a documented serum follicle stimulating hormone (FSH) level&#xD;
                  greater than 40mIU/mL.&#xD;
&#xD;
          -  Patients are excluded if they have active brain metastases or leptomeningeal&#xD;
             metastases. Subjects with brain metastases are eligible if metastases have been&#xD;
             treated and there is no magnetic resonance imaging (MRI) evidence of progression for 4&#xD;
             weeks or more after treatment is complete and within 28 days prior to the first dose&#xD;
             of nivolumab administration. There must also be no requirement for immunosuppressive&#xD;
             doses of systemic corticosteroids (&gt; 10 mg/day prednisone equivalents) for at least 2&#xD;
             weeks prior to study drug administration.&#xD;
&#xD;
          -  In order for patients with known history of testing positive for human&#xD;
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) to be&#xD;
             eligible, they must be on a stable highly active antiretroviral therapy (HAART)&#xD;
             regimen, have CD4 counts &gt; 350, with no detectable viral load on quantitative PCR.&#xD;
&#xD;
          -  Patients with treated hepatitis virus infections (Hepatitis B or Hepatitis C) are&#xD;
             eligible if they have been definitively treated for 6 months, have no detectable viral&#xD;
             load on quantitative PCR, and LFTs meet eligibility requirements.&#xD;
&#xD;
          -  Patients with active autoimmune disease or history of autoimmune disease that might&#xD;
             recur, which may affect vital organ function or require immune suppressive treatment&#xD;
             including systemic corticosteroids, should be excluded. These include but are not&#xD;
             limited to patients with a history of immune related neurologic disease, multiple&#xD;
             sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia&#xD;
             gravis; systemic autoimmune disease such as SLE, connective tissue diseases,&#xD;
             scleroderma, inflammatory bowel disease, Crohn's, ulcerative colitis, hepatitis; and&#xD;
             patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome,&#xD;
             or phospholipid syndrome should be excluded because of the risk of recurrence or&#xD;
             exacerbation of disease. Patient with vitiligo, endocrine deficiencies including&#xD;
             thyroiditis managed with replacement hormones including physiologic corticosteroids&#xD;
             are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's&#xD;
             syndrome and psoriasis controlled with topical medication and patients with positive&#xD;
             serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be&#xD;
             evaluated for the presence of target organ involvement and potential need for systemic&#xD;
             treatment but should otherwise be eligible.&#xD;
&#xD;
          -  Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,&#xD;
             residual hypothyroidism due to autoimmune condition only requiring hormone replacement&#xD;
             (such as Hashimoto's thyroiditis), psoriasis not requiring systemic treatment, or&#xD;
             conditions not expected to recur in the absence of an external trigger (precipitating&#xD;
             event).&#xD;
&#xD;
          -  Patients should be excluded if they have a condition requiring systemic treatment with&#xD;
             either corticosteroids (&gt;10 mg daily prednisone equivalents) or other&#xD;
             immunosuppressive medications within 14 days of study drug administration. Inhaled or&#xD;
             topical steroids and adrenal replacement doses &lt;10 mg daily prednisone equivalents are&#xD;
             permitted in the absence of active autoimmune disease. Patients are permitted to use&#xD;
             topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with&#xD;
             minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g.,&#xD;
             contrast dye allergy) or for treatment of non-autoimmune conditions (e.g.,&#xD;
             delayed-type hypersensitivity reaction caused by contact allergen) is permitted.&#xD;
&#xD;
          -  Any of the following within 2 months of registration: active peptic ulcer disease,&#xD;
             diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, malabsorption&#xD;
             syndrome. Any of the following within 6 months of registration: Intra-abdominal&#xD;
             abscess, gastrointestinal obstruction requiring parenteral hydration and/or nutrition,&#xD;
             gastrointestinal perforation. Note: complete resolution of an intra-abdominal abscess&#xD;
             must be confirmed prior to registration even if the abscess occurred more than 6&#xD;
             months prior to registration.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claire Friedman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2017</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nivolumab</keyword>
  <keyword>Paclitaxel</keyword>
  <keyword>Carboplatin</keyword>
  <keyword>17-182</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peritoneal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</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/NCT03245892
org study id: 17-182
nct id: NCT03245892
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to find out what effects, good or bad, the addition of nivolumab
      or the combination of nivolumab plus ipilimumab to typical chemotherapy has on the treatment
      of advanced high-grade serous cancers of ovarian, fallopian tube, or primary peritoneal
      origin. The typical chemotherapy treatment is Carboplatin and Paclitaxel.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Single center, non-randomized, open label, pilot study to evaluate the safety and tolerability of neoadjuvant and post-surgical dose dense paclitaxel and carboplatin chemotherapy in combination with nivolumab for the treatment of advanced high grade serous cancers of ovarian, fallopian tube, or primary peritoneal origin.
primary purpose: Treatment
masking: None (Open Label)
measure: number of patients with dose limiting toxicities with weekly paclitaxel/carboplatin plus nivolumab
time frame: 6 weeks
description: The safety of this regimen will be assessed by determination of the DLTs observed in the study population. If >=3/10 DLTs are seen we will deem the regimen not safe and stop the trial early. If >=5/20 patients have DLTs the treatment regimen would be deemed unsafe. Enrollment will be halted after 10 patients have accrued until all 10 patients have cleared the DLT period of 6 weeks
measure: number of patients with dose limiting toxicities weekly paclitaxel/carboplatin plus nivolumab and ipilimumab
time frame: 6 weeks
description: The safety of this regimen will be assessed by determination of the DLTs observed in the study population. If >=3/10 DLTs are seen we will deem the regimen not safe and stop the trial early. If >=5/20 patients have DLTs the treatment regimen would be deemed unsafe. Enrollment will be halted after 10 patients have accrued until all 10 patients have cleared the DLT period of 6 weeks
arm group label: Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)
arm group type: Experimental
description: Patients will be treated with nivolumab plus standard of care dose dense paclitaxel and carboplatin for three cycles, where each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen administered as adjuvant treatment. Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle. Carboplatin dose calculation instructions can be found in Appendix 4. Nivolumab 360mg will be infused IV over approximately 30min on Day 1 of Cycles 1-6. During the maintenance phase, Nivolumab 480mg will be infused IV on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks.
arm group label: Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin
arm group type: Experimental
description: Patients will be treated with nivolumab plus ipilimumab plus standard of care dose dense paclitaxel & carboplatin chemotherapy for 3 cycles (up to a maximum of six), each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen. Paclitaxel 80mg/m2 IV will be administered over approx 1 hour on Days 1,8, & 15 of each 21 day cycle. Carboplatin AUC6 will be administered as an approx 30 minute IV infusion, following paclitaxel admin on Day 1 of each 21 day cycle. Nivolumab 360mg will be infused IV over approx 30 min on Day 1 of Cycles 1-6 (to 9) of each 21 day cycle. Ipilimumab 1mg/kg will be infused IV over approx 30 min on Day 1 of Cycles 1 & 3, as well as Cycle 4 & Cycle 6. Of note, if patients receive more than 3 cycles in the pre-operative setting, then ipilimumab will be administered with the first & third cycle in the post-operative setting. Nivolumab will then be infused Day 1 of each 28 day maintenance phase cycle.
intervention type: Drug
intervention name: Carboplatin and Paclitaxel
description: Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle.
arm group label: Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)
arm group label: Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab 360mg will be infused IV over approximately 30 min on Day 1 of Cycles 1-6 (to 8) of each 21 day cycle. During the maintenance phase, Nivolumab 480mg will be infused IV over approximately 30 min on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks
arm group label: Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)
arm group label: Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin
intervention type: Procedure
intervention name: Cytoreductive surgery
description: Cytoreductive surgery
arm group label: Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)
arm group label: Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin
intervention type: Drug
intervention name: Ipilimumab
description: Ipilimumab 1mg/kg every 6 weeks x 3-6 cycles in the neoadjuvant setting (maximum 2 doses of ipilimumab)
arm group label: Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Claire Friedman
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Peritoneal Neoplasms
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Nivolumab
mesh term: Ipilimumab