NCT04751370

Testing Nivolumab and Ipilimumab With Short-Course Radiation in Locally Advanced Rectal Cancer

A Phase II Study of Neoadjuvant Nivolumab Plus Ipilimumab and Short-Course Radiation in MSI-H/dMMR Locally Advanced Rectal Adenocarcinoma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial investigates the effect of nivolumab and ipilimumab when given together with short-course radiation therapy in treating patients with rectal cancer that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with 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. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may kill more cancer cells.

Detailed description

PRIMARY OBJECTIVE: I. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve the pathologic complete response rate (pCR) in microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) locally advanced rectal adenocarcinoma at total mesorectal excision (TME). SECONDARY OBJECTIVES: I. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve the rate of sphincter preservation in low-lying tumors. II. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve 5-year disease-free survival (DFS). III. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve overall survival (OS). IV. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will have acceptable safety/toxicity. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 28 days for 2 cycles. Starting at least 2 weeks but no longer than 6 weeks after completion of cycle 2 of nivolumab and ipilimumab, patients undergo short-course radiation therapy of 5 fractions daily for 1 week. Patients then continue to receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. 8-12 weeks after completion of 4th cycle of nivolumab and ipilimumab, patients undergo TME. Patients also undergo magnetic resonance imaging (MRI) and computed tomography (CT) prior to TME and during follow up, and undergo sigmoidoscopy prior to TME. After completion of study treatment, patients are followed up for 5 years.

Conditions

• Locally Advanced Rectal Adenocarcinoma
• Stage II Rectal Cancer AJCC v8
• Stage III Rectal Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Computed Tomography	Undergo CT
BIOLOGICAL	Ipilimumab	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Nivolumab	Given IV
RADIATION	Radiation Therapy	Undergo short-course radiation therapy
PROCEDURE	Sigmoidoscopy	Undergo sigmoidoscopy
PROCEDURE	Total Mesorectal Excision	Undergo TME

Timeline

• Start date: 2022-02-08
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2021-02-12
• Last updated: 2026-04-13

Locations

216 sites across 1 country: United States

Regulatory

• FDA-regulated drug study