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

Conditions

• Endometrial Adenocarcinoma
• Endometrial Clear Cell Adenocarcinoma
• Endometrial Dedifferentiated Carcinoma
• Endometrial Endometrioid Adenocarcinoma
• Endometrial Mixed Cell Adenocarcinoma
• Endometrial Mucinous Adenocarcinoma
• Endometrial Undifferentiated Carcinoma
• Endometrioid Adenocarcinoma
• Recurrent Endometrial Carcinoma

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo collection of tissue and/or blood samples
• Computed Tomography — PROCEDURE
  Undergo CT
• Ipilimumab — BIOLOGICAL
  Given IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Nivolumab — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Jun 2, 2022

Status verified

Jun 2026

Primary completion

Jul 30, 2032

Completion

Jul 30, 2032

Study Design

Enrollment

81 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm I (nivolumab and ipilimumab)
  Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and ipilimumab IV over 90 minutes on day 1 of every other cycle. Cycles repeat every three weeks. Treatment with nivolumab and ipilimumab repeats for up to 8 cycles in the absence of disease progression, unacceptable toxicity, or CR. Patients then receive nivolumab alone on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression, unacceptable toxicity, or CR. MAINTENANCE THERAPY: Patients achieving CR receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. Patients also undergo CT scan and/or MRI throughout the trial.
• Active Comparator: Arm II (nivolumab)
  Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for up to 8 cycles, then every 4 weeks thereafter in the absence of disease progression, unacceptable toxicity, or CR. MAINTENANCE THERAPY: Patients achieving CR receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. Patients also undergo CT scan and/or MRI throughout the trial.

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years after randomization ]

Locations (137)

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