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

Memorial Sloan Kettering Cancer Center8 sites in 1 country35 target enrollmentAugust 3, 2017

ConditionsUterine Cancer Endometrial Carcinoma Carcinosarcoma Leiomyosarcoma Undifferentiated Sarcoma High Grade Endometrial Stromal Sarcoma Clear Cell Carcinoma

InterventionsNivolumab

DrugsNivolumab

Overview

Phase: Phase 2
Intervention: Nivolumab
Conditions: Uterine Cancer
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 35
Locations: 8
Primary Endpoint: Progression-Free Survival
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 3, 2017

End Date

April 1, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

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:
•MSI-high, or
•MMR-deficient, or
•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

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

Arms & Interventions

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.

Intervention: Nivolumab

Outcomes

Primary Outcomes

Progression-Free Survival

Time Frame: 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)