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

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ClinicalTrials.gov Identifier: NCT03508570
Recruitment Status : Not yet recruiting
First Posted : April 25, 2018
Last Update Posted : April 25, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

April 16, 2018
April 25, 2018
April 25, 2018
May 15, 2018
January 1, 2020   (Final data collection date for primary outcome measure)
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 =< 40%. Dose-finding for the combination of ipilimumab plus nivolumab will be done using the data-augmentation continuous reassessment method (DA-CRM).
Same as current
No Changes Posted
  • PK Parameters [ Time Frame: 6 weeks ]
    Serum concentration data over time used to characterize the PK of nivolumab and ipilimumab following the first dose of nivolumab or nivolumab+ipilimumab.
  • Clinical Benefit Rate [ Time Frame: 12 weeks ]
    Clinical benefit rate defined as the proportion of patients who achieve CR, PR, or SD as their best objective response determine by modified RECIST v1.1.
Same as current
Not Provided
Not Provided
 
Nivolumab With or Without Ipilimumab in Treating Participants 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
This phase Ib trial studies the side effects and best dose of nivolumab with or without ipilimumab in treating participants with female reproductive cancer that has come back or is high grade and has spread extensively throughout the peritoneal cavity. Monoclonal antibodies, such as ipilimumab and nivolumab, may interfere with the ability of tumor cells to grow and spread.

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. Participants are assigned to 1 of 2 groups.

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

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

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

Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Malignant Peritoneal Neoplasm
  • Malignant Retroperitoneal Neoplasm
  • Peritoneal Carcinomatosis
  • Recurrent Cervical Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Recurrent Uterine Corpus 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 IV Uterine Corpus 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 IVA Uterine Corpus 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
  • Stage IVB Uterine Corpus Cancer AJCC v8
  • Biological: Ipilimumab
    Given i.p.
    Other Names:
    • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
    • BMS-734016
    • MDX-010
    • MDX-CTLA4
    • Yervoy
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Nivolumab
    Given i.p.
    Other Names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
  • Other: Pharmacokinetic Study
    Correlative studies
    Other Names:
    • PHARMACOKINETIC
    • PK Study
  • Experimental: Group I (nivolumab)
    Participants receive nivolumab i.p. over 90 minutes on days 1, 15, and 29. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
    • Other: Pharmacokinetic Study
  • Experimental: Group II (nivolumab and ipilimumab)
    Participants receive nivolumab as in group I and ipilimumab i.p. on day 1. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Ipilimumab
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
    • Other: Pharmacokinetic Study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
58
Same as current
January 1, 2020
January 1, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with 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 are 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
  • 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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Amir Jazaeri 713-745-1613 CR_Study_Registration@mdanderson.org
United States
 
 
NCT03508570
2017-0264
NCI-2018-00282 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0264 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Amir Jazaeri M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP