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

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorNational Cancer Institute (NCI)

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

81 Participants
are divided into 2 treatment groups

Sponsors and collaborators