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

May 19, 2025 updated by: M.D. Anderson Cancer Center

Phase Ib Clinical Investigation of Intraperitoneal Ipilimumab and Nivolumab in Patients With Peritoneal Carcinomatosis Due to Gynecologic Cancers

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

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.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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), but do not require second-line treatment to be eligible for the dose-finding phase; eligibility 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 or have developed platinum resistant disease after frontline therapy (in which case progression on a second line therapy will not be required); 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)
  • Serum creatinine clearance (CL) >= 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
  • 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 immune checkpoint inhibitor therapy
  • 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
  • Active 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group I (nivolumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacokinetic Study
Correlative studies
Other Names:
  • PHARMACOKINETIC
  • PK Study
Biological: Nivolumab
Given i.p.
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
Experimental: Group II (nivolumab and ipilimumab)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacokinetic Study
Correlative studies
Other Names:
  • PHARMACOKINETIC
  • PK Study
Biological: Nivolumab
Given i.p.
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
Biological: Ipilimumab
Given i.p.
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)/recommended phase II dose (RP2D) of intraperitoneal (i.p.) nivolumab in combination with ipilimumab
Time Frame: 12 weeks
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).
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Amir A Jazaeri, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2018

Primary Completion (Actual)

November 11, 2024

Study Completion (Actual)

November 11, 2024

Study Registration Dates

First Submitted

April 16, 2018

First Submitted That Met QC Criteria

April 16, 2018

First Posted (Actual)

April 25, 2018

Study Record Updates

Last Update Posted (Actual)

May 22, 2025

Last Update Submitted That Met QC Criteria

May 19, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-0264 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2018-00282 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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