About this trial
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.
Eligibility criteria
Qualifiers
Patients with measurable or non-measurable (detectable) recurrent endometrial cancer
Measurable disease will be defined and monitored by RECIST v 1.1. Measurable disease is defined per RECIST 1.1 criteria as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
All other lesions (or sites of disease), including small lesions (longest diameter <10 mm or pathological lymph nodes with >= 10 to < 15 mm short axis), are considered non-measurable disease
Ascites and/or pleural effusion attributed to tumor
Disqualifiers
Patients with a diagnosis of endometrial serous carcinoma or carcinosarcoma
Patients who received prior anti-PD1/PD-L1 therapy and had grade 3-4 or recurring grade 2 immune-related toxicities that led to dose delay or discontinuation of immunotherapy due to those toxicities
Patients who received anti-CTLA-4 therapy or other immunotherapeutic agents
Patients on chronic steroid therapy except those on replacement therapy at a daily dose of 10mg or less prednisone or equivalent
Trial design
Treatments tested in this trial
- Biospecimen Collection
- Computed Tomography
- Ipilimumab
- Magnetic Resonance Imaging
- Nivolumab
Treatment groups
Sponsors and collaborators
National Cancer Institute (NCI)
Lead sponsor
NRG Oncology
Collaborator