Testing Nivolumab With or Without Ipilimumab in Deficient Mismatch Repair System (dMMR) Recurrent Endometrial Carcinoma

Study Summary

This phase II trial tests whether the combination of nivolumab and ipilimumab is better than nivolumab alone to shrink tumors in patients with deficient mismatch repair system (dMMR) endometrial carcinoma that has come back after a period of time during which the cancer could not be detected (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing damaged DNA. In 2-3% of endometrial cancers this may be due to a hereditary condition resulted from gene mutation called Lynch Syndrome (previously called hereditary nonpolyposis colorectal cancer or HNPCC). MMR deficient cells usually have many DNA mutations. Tumors that have evidence of mismatch repair deficiency tend to be more sensitive to immunotherapy. There is some evidence that nivolumab with ipilimumab can shrink or stabilize cancers with deficient mismatch repair system. However, it is not known whether this will happen in endometrial cancer; therefore, this study is designed to answer that question. 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. Giving nivolumab in combination with ipilimumab may be better than nivolumab alone in treating dMMR recurrent endometrial carcinoma.

Primary Outcome

The statistical test used for decision making is the stratified, standardized log-rank test (Z) based on PFS. For the safety lead-in analysis, the primary endpoint is the observation of at least one dose-limiting toxicity (DLT) in the first 3 cycles of treatment. Patients are classified as having a DLT in 3 cycles or receiving adequate treatment.

Conditions Studied

Interventions

• PROCEDURE Biospecimen Collection
• PROCEDURE Computed Tomography
• PROCEDURE Magnetic Resonance Imaging
• BIOLOGICAL Nivolumab
• BIOLOGICAL Ipilimumab

Study Locations (20)