Nivolumab With or Without Ipilimumab in Treating Patients With Recurrent or High Grade Gynecologic Cancer With Metastatic Peritoneal Carcinomatosis
Phase Ib Clinical Investigation of Intraperitoneal Ipilimumab and Nivolumab in Patients With Peritoneal Carcinomatosis Due to Gynecologic Cancers
2 other identifiers
interventional
26
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 16, 2018
CompletedFirst Posted
Study publicly available on registry
April 25, 2018
CompletedStudy Start
First participant enrolled
September 21, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
November 11, 2024
CompletedMay 22, 2025
May 1, 2025
6.1 years
April 16, 2018
May 19, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose (MTD)/recommended phase II dose (RP2D) of intraperitoneal (i.p.) nivolumab in combination with ipilimumab
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
Study Arms (2)
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.
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.
Interventions
Given i.p.
Correlative studies
Given i.p.
Correlative studies
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Knisely A, Hinchcliff E, Fellman B, Mosley A, Lito K, Hull S, Westin SN, Sood AK, Schmeler KM, Taylor JS, Huang SY, Sheth RA, Lu KH, Jazaeri AA. Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis. Med. 2024 Apr 12;5(4):311-320.e3. doi: 10.1016/j.medj.2024.02.003. Epub 2024 Mar 11.
PMID: 38471508BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amir A Jazaeri
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 16, 2018
First Posted
April 25, 2018
Study Start
September 21, 2018
Primary Completion
November 11, 2024
Study Completion
November 11, 2024
Last Updated
May 22, 2025
Record last verified: 2025-05