Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Adenocarcinoma

Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Herbal and Botanical

Antibodies

Antibodies, Monoclonal

Cetuximab

Immunoglobulins

Antineoplastic Agents, Immunological

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

Behaviors and Mental Disorders

Financial Stress

Rectal Neoplasms

Rectal Diseases

Stress, Psychological

Behavioral Symptoms

Patients complete questionnaires over 20-60 minutes at baseline and at 3, 6, 12, and 24 months after cancer diagnosis.

Quality-of-Life Assessment

Questionnaire Administration

Sheetal Kircher

This research trial studies the financial burden in patients with stage I-III colon or rectal cancer who are undergoing treatment. Collecting data from patients about their cost and quality of life may help doctors to better understand the impact of cancer treatment on a patient?s employment and finances.

PRIMARY OBJECTIVES:

I. Evaluate the change in level of self-reported financial burden from baseline (within 60 days of diagnosis) to 12 months after diagnosis of colon or rectal cancer treated with curative-intent.

SECONDARY OBJECTVIES:

I. Evaluate reported access and utilization of financial services (i.e. financial counselor, navigator, social workers) and its association to financial burden in the first 12 months after diagnosis of colon or rectal cancer treated with curative-intent.

II. Evaluate the change in level of self-reported financial burden and employment limitations from baseline (within 60 days of diagnosis) to 3, 6, and 12 months after diagnosis of colon or rectal cancer treated with curative-intent.

III. Evaluate long term outcomes at 24 months after diagnosis including financial burden, employment limitations and adherence to clinical follow-up guidelines.

IV. Evaluate the change of quality-of-life outcome (QoL) from baseline to 12 months and its association with predictors.

V. Evaluate the change in level of self-reported financial burden from baseline to 12 months using alternate measures of financial burden (i.e. impact of cost questions and single item from European Organization for Research and Treatment of Cancer \[EORTC\] questionnaire \[Q\]30).

OUTLINE:

Patients complete questionnaires over 20-60 minutes at baseline and at 3, 6, 12, and 24 months after cancer diagnosis.

Financial Burden Assessment in Patients With Stage I-III Colon or Rectal Cancer Undergoing Treatment

Longitudinal Assessment of Financial Burden in Patients With Colon or Rectal Cancer Treated With Curative Intent

Will calculate the difference of Comprehensive Score for Financial Toxicity (COST) measurements from baseline to 12-month follow up for the completers who provide data at both time points, and use the paired t-test to assess if the mean difference is significantly different from zero. In case the data are not normally distributed, nonparametric methods (e.g., Wilcoxon signed-rank test) will be used instead to assess the difference. In addition, linear regression models with the change of COST from baseline to 12-month follow up as the response variable will be fit to investigate the impact of other factors, including demographics variables (e.g., age, sex, marital status), clinical variables (e.g., stage of disease, malignancy type, chemotherapy status), baseline questionnaire variables (e.g., self-efficacy,). The three-level treatment status (intravenous \[IV\] chemotherapy, chemotherapy without IV, and no chemotherapy) will also be evaluated as a predictor.

Will evaluate reported access and utilization of financial services (i.e. financial counselor, navigator, social workers) and its association to financial burden in the first 12 months after diagnosis of colon or rectal cancer treated with curative-intent. Will be assessed by Consumer Based Cancer Care Value Index (CCVI). For the continuous item variable, will conduct the paired t test to examine the difference if the distribution is normal. If not normally distributed, Wilcoxon signed rank test will be used. For the categorical item variable, the paired proportion test (e.g., McNemar test) will be used instead. The association between CCVI and COST measures will be evaluated using the Pearson or Spearman correlation coefficient.

Will be assessed by Work Productivity and Activity Impairment Questionnaire, Work Ability Index, and Work after cancer survey. If the distributions are normal, will conduct the paired t tests to examine the differences of these variables. If not normally distributed, Wilcoxon signed rank tests will be used. The association with COST measures will be evaluated using the Pearson or Spearman correlation coefficients.

Will evaluate long term outcomes at 24 months after diagnosis for adherence to clinical follow-up guidelines. Specially, linear (or generalized linear) mixed model will be fit to study the change in the mean response over time. In case the changes in the mean response over time are not linear, the quadratic trends or non-linear trends via spline may be considered in the modeling. Interactions will be evaluated as well.

Will evaluate long term outcomes at 24 months after diagnosis for financial burden. Specially, linear (or generalized linear) mixed model will be fit to study the change in the mean response over time and also the effects of cancer type, stage, treatment plan and demographics, etc. on financial burden. In case the changes in the mean response over time are not linear, the quadratic trends or non-linear trends via spline may be considered in the modeling. Interactions will be evaluated as well.

Will evaluate long term outcomes at 24 months after diagnosis for employment limitations. Specially, linear (or generalized linear) mixed model will be fit to study the change in the mean response over time. In case the changes in the mean response over time are not linear, the quadratic trends or non-linear trends via spline may be considered in the modeling. Interactions will be evaluated as well.

Will evaluate the change of QoL from baseline to 12 months and its association with predictors. Will be evaluated by Functional Assessment of Cancer Therapy-General.

Will use alternate measures of financial burden (i.e. impact of cost questions and single item from European Organization for Research and Treatment of Cancer Questionnaire 30).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Financial Burden Assessment in Patients With Stage I-III Colon or Rectal Cancer Undergoing Treatment	NCT03516942	Stage I Colon C... Stage I Rectal ... Stage II Colon ... Stage II Rectal... Stage IIA Colon... Stage IIA Recta... Stage IIB Colon... Stage IIB Recta... Stage IIC Colon... Stage IIC Recta... Stage III Colon... Stage III Recta... Stage IIIA Colo... Stage IIIA Rect... Stage IIIB Colo... Stage IIIB Rect... Stage IIIC Colo... Stage IIIC Rect...	Quality-of-Life... Questionnaire A...	18 Years -	Eastern Cooperative Oncology Group

Spots Global Cancer Trial Database for stage iib colon cancer ajcc v8