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

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ClinicalTrials.gov Identifier: NCT03508570
Recruitment Status : Recruiting
First Posted : April 25, 2018
Last Update Posted : September 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Biological: Ipilimumab Other: Laboratory Biomarker Analysis Biological: Nivolumab Other: Pharmacokinetic Study Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Clinical Investigation of Intraperitoneal Ipilimumab and Nivolumab in Patients With Peritoneal Carcinomatosis Due to Gynecologic Cancers
Actual Study Start Date : September 21, 2018
Estimated Primary Completion Date : January 1, 2020
Estimated Study Completion Date : January 1, 2021


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

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 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.
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




Primary Outcome Measures :
  1. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03508570


Contacts
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Contact: Ljiljana Milojevic 713-792-8578 lmilojev@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Amir A. Jazaeri    713-745-1613      
Principal Investigator: Amir A. Jazaeri         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amir A Jazaeri M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03508570     History of Changes
Other Study ID Numbers: 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 )
First Posted: April 25, 2018    Key Record Dates
Last Update Posted: September 27, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Uterine Cervical Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endometrial Neoplasms
Retroperitoneal Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Nivolumab
Ipilimumab