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Cola

Patients receive encorafenib PO and cetuximab IV on study. Patients also undergo collection of blood samples throughout the study and CT or MRI during screening and follow-up.

Patients undergo observation per usual care on study. Patients also undergo collection of blood samples throughout the study and CT or MRI during screening and follow-up.

Encorafenib

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Patient Observation

Rona Yaeger, MD

Jamie Crawley

Site Public Contact

Gregory A. Masters

Olatunji B. Alese

Jared D. Acoba

John M. Schallenkamp

Alison K. Conlin

Bryan A. Faller

Chengwei Peng

Ardaman Shergill

Prem Sobti

Joshua Lukenbill

Deborah W. Wilbur

Elie G. Dib

Daniel Almquist

Daniel M. Anderson

Rona D. Yaeger

This phase II/III trial compares treatment with encorafenib and cetuximab to usual care (patient observation) for reducing the chance of cancer recurrence after standard surgery and chemotherapy in patients with BRAF-mutated stage IIB-III colon cancer. Encorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Giving encorafenib and cetuximab after standard surgery and chemotherapy may be more effective at reducing the chance of cancer recurrence compared to the usual patient observation.

The primary and secondary objectives of the study:

PRIMARY OBJECTIVES:

I. To evaluate and compare 6 month circulating tumor deoxyribonucleic acid (ctDNA) clearance rate in study patients with detectable ctDNA prior to randomization to targeted BRAF therapy versus usual care after standard adjuvant chemotherapy. (Phase II) II. To evaluate and compare 6 month ctDNA recurrence-free survival (ctDNA-RFS) rate in study patients with undetectable ctDNA prior to randomization to targeted BRAF therapy versus usual care after standard adjuvant chemotherapy. (Phase II) III. To evaluate and compare disease-free survival (DFS) (measured from randomization) in patients with resected stage III or high-risk (pT4) stage II mismatch repair protein (MMR) proficient BRAF V600E colon cancer treated with targeted BRAF therapy versus usual care after standard adjuvant chemotherapy. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate and compare overall survival (OS) between the two treatment arms.

II. To evaluate and compare the toxicity profile between the two treatment arms.

III. To evaluate and compare the alternative DFS endpoint (measured from date of primary tumor resection) between the two treatment arms.

IV. To evaluate and compare DFS in the subset of patients with detectable ctDNA prior to randomization between the two treatment arms.

EXPLORATORY OBJECTIVE:

I. To evaluate and compare patient-reported outcomes for symptoms of rash, diarrhea, and fatigue according to Patient Reported Outcomes Version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) between the two treatment arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive encorafenib orally (PO) and cetuximab intravenously (IV) on study. Patients also undergo collection of blood samples throughout the study and computed tomography (CT) or magnetic resonance imaging (MRI) during screening and follow-up.

ARM II: Patients undergo observation per usual care on study. Patients also undergo collection of blood samples throughout the study and CT or MRI during screening and follow-up.

Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer

Randomized Trial of Consolidation Targeted Adjuvant Therapy With Encorafenib and Cetuximab Versus Usual Care for Patients With Stage II/III BRAF V600E Colon Cancer

defined as the proportion of patients with undetectable ctDNA status at 6 months after randomization among patients with detectable ctDNA status at randomization. The ctDNA clearance rate at 6 months after randomization in experimental arm will be compared to control arm by Chi-squared test. The one-sided p-value will be reported. Due to small sample size, Cochran and Mantel-Haenszel test, stratified by stratification factors will be performed as sensitivity analysis.

Defined as the proportion of patients who remained undetectable ctDNA status, recurrence-free, and alive at 6 months after randomization among patients with undetectable ctDNA status at randomization. The ctDNA-RFS in experimental arm will be compared to control arm by Cochran and Mantel-Haenszel test, stratified by stratification factors. The one-sided p-value will be reported.

Defined as the time from the date of randomization to the date of first documented recurrence or death due to all cause, whichever occurs first. Patients without events observed at the end of the study will be censored at the date of last disease evaluation which shows no evidence of disease. At each analysis (Interim #1, Interim #2, and Final), stratified Cox model will be conducted to compare DFS in the experimental arm to DFS in the control arm with stratification factors as stratum, based on all data collected at the analysis time point.

Defined as the time from the date of randomization to death due to all causes. The distributions of time-to-event endpoints will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.

The maximum grade for each type of adverse events that are possibly, probably, or definitely related to study treatments will be summarized for each patient. The frequency tables will be reviewed to determine the patterns. The overall adverse event rates for grade 4 or higher adverse events will be compared between two treatment groups using Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).

Defined as the time from the date of primary tumor resection to the date of first documented recurrence or death due to all cause, whichever occurs first. The distributions of time-to-event endpoints will be estimated, in each arm, using the method of Kaplan-Meier and compared by a stratified Cox regression model.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer	NCT05710406	Colon Adenocarc... Microsatellite ... Stage IIB Colon... Stage IIC Colon... Stage III Colon...	Encorafenib Cetuximab Biospecimen Col... Computed Tomogr... Magnetic Resona... Patient Observa...	18 Years -	Alliance for Clinical Trials in Oncology
Testing the Use of BRAF-Targeted Therapy After Surgery and Usual Chemotherapy for BRAF-Mutated Colon Cancer	NCT05710406	Colon Adenocarc... Microsatellite ... Stage IIB Colon... Stage IIC Colon... Stage III Colon...	Encorafenib Cetuximab Biospecimen Col... Computed Tomogr... Magnetic Resona... Patient Observa...	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for microsatellite stable colon carcinoma