A Study of Nivolumab in Selected Uterine Cancer Patients

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03241745

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Locations

Arm

71.9

Anticipated Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test the safety of nivolumab and find out what affects, if any, nivolumab has on people and their risk of gynecologic cancer. The investigators also want to find out what effects, good or bad, nivolumab has on the patient and their cancer.

Condition or Disease	Intervention/Treatment	Phase
Uterine Cancer Endometrial Carcinoma Carcinosarcoma Leiomyosarcoma Undifferentiated Sarcoma High Grade Endometrial Stromal Sarcoma Clear Cell Carcinoma	Drug: Nivolumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an MSKCC investigator-initiated, single-center, non-randomized, open-label, phase 2 study.This is an MSKCC investigator-initiated, single-center, non-randomized, open-label, phase 2 study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Single-Agent Nivolumab in Patients With Microsatellite Unstable/Mismatch Repair Deficient/Hypermutated Uterine Cancer

Actual Study Start Date :

Aug 3, 2017

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab Nivolumab treatment: Nivolumab 480 mg IV once every 4 weeks. Treatment will continue until time of disease progression or until development of unacceptable toxicity, whichever comes first.	Drug: Nivolumab Nivolumab 480 mg IV once every 4 weeks

Arm

Intervention/Treatment

Experimental: Nivolumab

Nivolumab treatment: Nivolumab 480 mg IV once every 4 weeks. Treatment will continue until time of disease progression or until development of unacceptable toxicity, whichever comes first.

Drug: Nivolumab

Nivolumab 480 mg IV once every 4 weeks

Outcome Measures

Primary Outcome Measures

Progression-Free Survival [at 24 weeks]
will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of metastatic or recurrent uterine cancer (endometrial carcinoma, carcinosarcoma, clear cell carcinoma, leiomyosarcoma, undifferentiated sarcoma, high grade endometrial stromal sarcoma) by Memorial Sloan Kettering Cancer Center. Carcinosarcomas, endometrioid and clear cell carcinomas that appears to have arisen in the ovary/fallopian tube or peritoneum are also eligible. Recurrence should not be amenable to curative approaches such as surgical resection or chemoradiotherapy.
Tumor is confirmed to be one of the following: 1. MSI-high, or 2. MMR-deficient, or 3. Hypermutated defined as ≥20 somatic mutations in the tumor by MSK-IMPACT
One or more prior lines of cytotoxic treatment for advanced disease (prior hormonal therapy is not considered to count as prior lines of therapy)
Measurable disease by RECIST 1.1 criteria
No known CNS metastases
ECOG Performance status 0-1
ECOG Performance status 0-1
WBC ≥ 2000/uL, ANC ≥ 1500/uL, PLT ≥ 100,000/uL, HGB ≥ 8 g/dL
Serum creatinine ≤ 1.5 x ULN or creatinine clearance of ≥ 40mL/min by Cockroft-Gault formula
AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
Total bilirubin ≤ 1.5 x ULN, except subjects with Gilbert's syndrome who can have total bilirubin ≤ 3.0 mg/dL
Able to sign voluntary written informed consent
Female, 18 years of age or older
Available archival tumor tissue or patient is willing to undergo new biopsy
Premenopausal women of child bearing potential must have a normal urine or serum beta-HCG prior to enrollment, and must agree to use effective contraception during treatment with nivolumab and for at least 5 months following the last dose of nivolumab.

Exclusion Criteria:

Disease eligible for potentially curative treatment with standard chemotherapy, surgical resection, or chemoradiotherapy.
Known or suspected autoimmune disease, except for subjects with vitiligo, diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to an autoimmune immune condition only requiring thyroid hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
Serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control would be jeopardized by protocol therapy
History of bowel obstruction, refractory ascites, or bowel perforation due to advanced disease within the past 3 months from start of study treatment.
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways
Patients who have a condition that requires systemic treatment with either corticosteroids within 7 days of enrollment (systemic corticosteroid therapy is defined as >10 mg daily prednisone or its equivalent); or who require other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Prior history of malignancy or a concurrent malignancy, with the exception of cutaneous basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, or in situ carcinoma of the uterine cervix, prostate, or breast, unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
Breastfeeding women, pregnant women
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection (if patient has documented Hepatitis B and C from within 6 months of enrollment, these tests do not need to be repeated.)
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Known allergy or Adverse Drug Reaction to nivolumab, or a history of allergy to study drug components.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
8	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103