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Nivolumab With or Without Ipilimumab in Treating Patients With Recurrent or High Grade Gynecologic Cancer With Metastatic Peritoneal Carcinomatosis

NCT03508570

Description:

This phase Ib trial studies the side effects and best dose of nivolumab with or without ipilimumab in treating patients with female reproductive cancer that has come back (recurrent) or is high grade and has spread extensively throughout the peritoneal cavity (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Cervical Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab With or Without Ipilimumab in Treating Patients With Recurrent or High Grade Gynecologic Cancer With Metastatic Peritoneal Carcinomatosis
  • Official Title: Phase Ib Clinical Investigation of Intraperitoneal Ipilimumab and Nivolumab in Patients With Peritoneal Carcinomatosis Due to Gynecologic Cancers

Clinical Trial IDs

  • ORG STUDY ID: 2017-0264
  • SECONDARY ID: NCI-2018-00282
  • SECONDARY ID: 2017-0264
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03508570

Conditions

  • Malignant Peritoneal Neoplasm
  • Malignant Retroperitoneal Neoplasm
  • Peritoneal Carcinomatosis
  • Platinum-Resistant Fallopian Tube Carcinoma
  • Platinum-Resistant Ovarian Carcinoma
  • Platinum-Resistant Primary Peritoneal Carcinoma
  • Recurrent Cervical Carcinoma
  • Recurrent Endometrial Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Stage IV Cervical Cancer AJCC v8
  • Stage IV Fallopian Tube Cancer AJCC v8
  • Stage IV Ovarian Cancer AJCC v8
  • Stage IV Primary Peritoneal Cancer AJCC v8
  • Stage IVA Cervical Cancer AJCC v8
  • Stage IVA Fallopian Tube Cancer AJCC v8
  • Stage IVA Ovarian Cancer AJCC v8
  • Stage IVA Primary Peritoneal Cancer AJCC v8
  • Stage IVB Cervical Cancer AJCC v8
  • Stage IVB Fallopian Tube Cancer AJCC v8
  • Stage IVB Ovarian Cancer AJCC v8
  • Stage IVB Primary Peritoneal Cancer AJCC v8

Interventions

DrugSynonymsArms
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyGroup II (nivolumab and ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoGroup I (nivolumab)

Purpose

This phase Ib trial studies the side effects and best dose of nivolumab with or without ipilimumab in treating patients with female reproductive cancer that has come back or is high grade and has spread extensively throughout the peritoneal cavity. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the recommended phase II dose (RP2D) of intraperitoneal (i.p.) nivolumab in
      combination with ipilimumab.

      SECONDARY OBJECTIVES:

      I. To describe the pharmacokinetics (PK), toxicities, and immune-related adverse events
      associated with i.p. checkpoint inhibitor therapy.

      II. To estimate the clinical benefit rate (rate of partial response [PR], complete response
      [CR], and stable disease [SD] using Response Evaluation Criteria in Solid Tumors [RECIST]
      version 1.1 modified to include immune-related response criteria) for the expansion cohort.

      EXPLORATORY OBJECTIVES:

      I. To determine blood based transcriptional changes associated with pharmacokinetics (PK)
      time points and determine their correlation with serum drug concentrations, clinical
      response, and immune related adverse events.

      II. To determine baseline and on-treatment molecular alteration (ribonucleic acid [RNA] and
      protein) associated with i.p. and nivolumab (Nivo) (for the expansion cohort).

      OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 groups.

      GROUP I: Patients receive nivolumab i.p. over 90 minutes on days 1, 15, and 29. Cycles repeat
      every 6 weeks in the absence of disease progression or unacceptable toxicity.

      GROUP II: Patients receive nivolumab as in group I and ipilimumab i.p. on day 1. Cycles
      repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

      After completion of the study treatment, patients are followed up every 6 weeks for at least
      100 days.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (nivolumab)ExperimentalPatients receive nivolumab i.p. over 90 minutes on days 1, 15, and 29. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
Group II (nivolumab and ipilimumab)ExperimentalPatients receive nivolumab as in group I and ipilimumab i.p. on day 1. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have biopsy-confirmed ovarian or other gynecologic cancers (fallopian
             tube, peritoneal, endometrial, or cervical cancer) who have recurred after or
             progressed on frontline and one or more second-line standard treatments; patients with
             ovarian/fallopian tube/peritoneal cancers must have platinum refractory or resistant
             disease (defined as progression on a platinum containing regimen or recurrence within
             180 days of prior dose of platinum-containing regimen) to be eligible for the
             dose-finding phase; enrollment for the expansion cohort will be limited to subjects
             with high grade epithelial ovarian, fallopian tube, or peritoneal carcinomas who have
             recurred after or progressed on frontline and one or more second-line standard
             treatments; however, for the dose expansion phase, potential subjects are not required
             to have platinum refractory or resistant disease

          -  Measurable metastatic disease (by RECIST version [v] 1.1) in the peritoneal cavity or
             retroperitoneal lymph nodes; disease outside of the peritoneal cavity is allowed as
             long as metastatic sites are also present within the peritoneum/retroperitoneum

          -  Absolute neutrophil count >= 1500/mL

          -  Platelets >= 100,000/mL

          -  Hemoglobin >= 9 g/dL (transfusion to meet this criterion is allowed)

          -  Creatinine clearance >= 50 mL/min (using Cockcroft-Gault)

          -  Total bilirubin =< 1.5 X upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             ULN (=< 5 X ULN in subjects with bone or liver metastases)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

          -  Subjects must be >= 4 weeks beyond treatment with any chemotherapy or other
             investigational therapy to include hormonal, biological, or targeted agents (>= 8
             weeks from previous bevacizumab treatment) at the time of first dose of study drug(s)

          -  Women of child-bearing potential MUST have a negative serum human chorionic
             gonadotropin (HCG) test unless prior hysterectomy or menopause (defined as 12
             consecutive months of amenorrhea); subjects are considered not to be of child-bearing
             potential if they are surgically sterilized or post-menopausal (>= 50 years of age and
             has not had menses for greater than 1 year or with serum follicle stimulating hormone
             (FSH) in the menopausal range will be considered postmenopausal); subjects should not
             become pregnant or breastfeed while on this study; sexually active subjects of child
             bearing potential must agree to use contraception for the duration of study
             participation and for 5 months after the last dose of ipilimumab or nivolumab

          -  Ability to understand and willingness to sign informed consent form prior to
             initiation of the study and any study procedures

          -  Subjects in expansion cohort only: Willing to undergo pre- and on-treatment biopsies

        Exclusion Criteria:

          -  Patients who are pregnant or breastfeeding

          -  Patients with low grade ovarian/fallopian tube/peritoneal cancers

          -  Prior immunotherapy with checkpoint inhibitors

          -  History of inflammatory bowel disease (including ulcerative colitis and Crohn's
             disease), or any other known autoimmune diseases including rheumatoid arthritis,
             scleroderma, systemic lupus erythematosus, and autoimmune vasculitis

          -  History of previous malignancy that in the principal investigator (PI)'s opinion has a
             reasonable chance of recurrence during the study period or otherwise confounding this
             clinical trial

          -  History of peritonitis or diverticulitis

          -  Patients requiring corticosteroids use at doses greater than prednisone 10 mg daily
             equivalent (use of inhaled steroids, and short-term steroid for radiologic contrast
             allergy, or treatment of immune-related adverse events are allowed)

          -  Medical or surgical history that in the treating physician's opinion would make the
             subject not a suitable candidate for i.p. therapy; examples would include surgically
             documented extensive intraperitoneal adhesions or large volume ascites

          -  History of chronic obstructive pulmonary disease (COPD) or other chronic pulmonary
             disease requiring systemic steroid therapy, oxygen, or hospitalization

          -  Chronic hepatitis B or C virus infection, or known human immunodeficiency virus (HIV)
             positive, that might affect host immunity

          -  Any other illness or condition that in the investigator's opinion would adversely
             affect the safety of checkpoint inhibitor therapy

          -  Active infection requiring intravenous (IV) antibiotics or other uncontrolled
             intercurrent illness requiring hospitalization

          -  Inability to comply with the study and follow-up procedures

          -  History of cerebrovascular accident, myocardial infarction or unstable angina within
             the previous 6 months before starting therapy

          -  Prolongation of QT interval (QT)/corrected QT interval (QTc) (QTc interval > 470 ms)
             using the Fridericia method of QTc analysis

          -  Known active central nervous system metastases and/or carcinomatous meningitis

          -  History of severe hypersensitivity reaction with biologics therapy (monoclonal
             antibodies)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)/recommended phase II dose (RP2D) of intraperitoneal (i.p.) nivolumab in combination with ipilimumab
Time Frame:12 weeks
Safety Issue:
Description:The RP2D or the MTD is defined as the combination of ipilimumab + nivolumab with the dose limiting toxicity (DLT) rate =< 30%. Dose-finding for the combination of ipilimumab plus nivolumab will be done using the data-augmentation continuous reassessment method (DA-CRM).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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