Biomarkers in Predicting Response to Cetuximab in Patients With Advanced Colorectal Cancer

Evaluating BRAF Mutations as Predictors of Efficacy in Cetuximab-Treated Colorectal Cancer Patients: A Retrospective Study of Tissues From CALGB / SWOG

RATIONALE: Studying samples of tissue in the laboratory from patients who received cetuximab may help doctors understand and predict how well patients will respond to treatment.

PURPOSE: This research study is studying biomarkers in predicting response to cetuximab in patients with advanced colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Genetic: mutation analysis

Detailed Description

OBJECTIVES:

Primary

• To determine, among patients with advanced CRC, whether the effect of treatment (cetuximab vs bevacizumab) on progression-free survival (PFS) depends on tumor BRAF V600E mutational status.

Secondary

• To study the relationships between tumor BRAF V600E mutational status, OS, and tumor response.

OUTLINE: This is a multicenter study.

Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405.

• Study Type: Observational
• Enrollment (Anticipated): 1142

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients previously enrolled on CALGB-C80405 who have KRAS WT or KRAS mut tumor and have been randomized to treatment with either bevacizumab or cetuximab alone in a primary care clinic setting.

Description

DISEASE CHARACTERISTICS:

• Participation in CALGB-C80405

  • Have KRAS WT or KRAS mut tumor

  • Randomized to treatment with either bevacizumab or cetuximab alone

    • Patients randomized to the combination therapy are not eligible
• Available specimens at the PCO for BRAF mutation detection
• Patient consent for use of samples

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Correlative (BRAF V600E mutation analysis); Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. Mutation status is correlated with clinical response and outcome data from patients enrolled on CALGB-C80405.	Other: laboratory biomarker analysis; Genetic: mutation analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival as measured by RECIST	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 36 months
tumor response as measured by RECIST	Up to 36 months

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Najjia N. Mahmoud, MD, Abramson Cancer Center of the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2009
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; stage III rectal cancer; stage IIIA colon cancer; stage IIIB colon cancer; stage IIIC colon cancer; stage IVA colon cancer; stage IVB colon cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CALGB-SWOG-150506-80405-BRAF; CDR0000688745 (Registry Identifier: NCI Physician Data Query)