Trials / Active Not Recruiting

Active Not RecruitingNCT05308446

Testing the Addition of Nivolumab to Standard Treatment for Patients With Metastatic or Unresectable Colorectal Cancer That Have a BRAF Mutation

Randomized Phase II Trial of Encorafenib and Cetuximab With or Without Nivolumab (NSC #748726) for Patients With Previously Treated, Microsatellite Stable, BRAFV600E Metastatic and/or Unresectable Colorectal Cancer

Status: Active Not Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 84 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial tests whether adding nivolumab to the usual treatment (encorafenib and cetuximab) works better than the usual treatment alone to shrink tumors in patients with colorectal cancer that has spread to other places in the body (metastatic) or that cannot be removed by surgery (unresectable) and whose tumor has a mutation in a gene called BRAF. Encorafenib is in a class of medications called kinase inhibitors. It is used in patients whose cancer has a certain mutation (change) in the BRAF gene. It works by blocking the action of mutated BRAF that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, 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 encorafenib and cetuximab may be more effective than encorafenib and cetuximab alone at stopping tumor growth and spreading in patients with metastatic or unresectable BRAF-mutant colorectal cancer.

Detailed description

PRIMARY OBJECTIVE: I. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with microsatellite stable (MSS), BRAF\^V600E metastatic and/or unresectable colorectal cancer (CRC) randomized to treatment with nivolumab + encorafenib + cetuximab compared to encorafenib + cetuximab. SECONDARY OBJECTIVES: I. To compare overall response rate (ORR), including confirmed and unconfirmed, complete and partial response, according to RECIST 1.1 criteria between the two arms. II. To compare overall survival (OS) between the two arms. III. To compare duration of response between the two arms. IV. To compare safety and tolerability between the two arms. V. To assess immune-related PFS using modified response criteria adapted for immunotherapy (irRC-PFS) in patients treated with nivolumab + encorafenib + cetuximab. BANKING OBJECTIVE: I. To bank tissue and blood specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, cetuximab intravenously (IV) on days 1 and 15, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive encorafenib PO QD on days 1-28 and cetuximab IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed until death or 3 years after registration, whichever occurs first.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Cetuximab	Given IV
DRUG	Encorafenib	Given PO
BIOLOGICAL	Nivolumab	Given IV

Timeline

Start date: 2022-07-19
Primary completion: 2026-09-30
Completion: 2026-09-30
First posted: 2022-04-04
Last updated: 2026-04-13

Locations

286 sites across 2 countries: United States, Puerto Rico

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05308446. Inclusion in this directory is not an endorsement.