Encorafenib Plus Cetuximab in a Neoadjuvant Setting in Patients With BRAF Mutation Localised Colon or Upper Rectum Cancer

NCT05706779 | Recruiting Phase 2 DMC

• 1 other identifier: FFCD 2006 NEORAF
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot trial which aims to assess the concept of anti-BRAF neoadjuvant treatment (encorafenib) in combination with cetuximab in patients with colon cancer or rT3/T4 supra-peritoneal upper rectal cancer based on a pre-operative CT-scan. About 10% of patients will have a mutated BRAF V600E tumour and the objective is to include 30 patients with this mutation. If the tumour is not confirmed as a carrier of the BRAF V600E mutation or has an RAS mutation according to centralised assessment, treatment will be discontinued in this patient and cancer surgery will be organised as soon as possible. The patient will be excluded from the statistical analysis and will be replaced by a new patient in order to obtain 30 patients with confirmed BRAF V600E mutation and RAS wild type . It should be noted that less than a 3% discrepancy between the numbers of local laboratory results and central analysis results, has been reported in over 600 BRAF V600E mutated colon cancers in the BEACON CRC study. Based on these figures, there should be 0 or 1 patient with discrepant results in the study presented here. Furthermore, in the hypothetical case of a patient who is an early permanent discontinuation of the study prior to surgery, this patient will be replaced in order to obtain a total of 30 patients who underwent surgery after neoadjuvant treatment.

Conditions

Colorectal Cancer; BRAF V600E Mutation Positive

Outcome Measures

Primary Outcomes (1)

• To assess the rate of significant tumour regression (TRG 0 to 2 according to Ryan's modified score of the AJCC 2010)

  with centralised review after neoadjuvant treatment with encorafenib and cetuximab, in patients with RAS wild type localised colon or upper rectum cancer (CC) and carriers of the BRAF V600E mutation.

  6 months after completing inclusions

Study Arms (1)

Encorafenib + Cetuximab

EXPERIMENTAL

Drug: Encorafenib Oral Capsule + Cetuximab

Interventions

Encorafenib Oral Capsule + Cetuximab DRUG

Encorafenib: 4 capsules 75 mg/day (300 mg) , 7 days/7 during 6 weeks Cetuximab: 500mg/m2 intravenous route every 2 weeks (D1, D14, D28), for 3 cycles over 4 weeks.

Encorafenib + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent signed and dated by the patient and the investigator
• Age ≥18 years at time of informed consent
• Adenocarcinoma of the colon or of the upper rectum (supra-peritoneal) considered operable and histologically confirmed, localised, mutated BRAF V600E determined in a biopsy specimen and resectable after CT-scan assessment.
• Remark: Centralised analysis of BRAF status will be performed in order to confirm the existence of the mutation concomitantly with the 1st cycle of therapy
• Tumour stage rT4 or rT3 with ≥ 5 mm extra-mural extension in a CT-scan.
• rT3 with high risk: Tumour spread from the peripheral serosa and extension to the adjacent peritoneal fat of more than 5 mm in its longest diameter (both axial and coronal planes)
• rT4: Extension to an adjacent organ
• Patient able to provide a sufficient quantity of representative tumour sample (slides or extracted tumor DNA) for centralised analysis of RAS and BRAF mutational status.
• WHO performance status 0 or 1
• Haematological function considered satisfactory:
• Polymorphonuclear neutrophils (PMN) ≥ 1,500/mm3
• Platelets ≥ 100,000/mm3
• Hb ≥ 9g/dL
• Creatinine clearance \> 50 mL/min (according to MDRD formula).
• Serum levels of magnesium within normal limits of the centre.

You may not qualify if:

• Existence of distant metastases or adjacent nodules of peritoneal carcinosis (M1).
• Existence of a dual-tumour location.
• known RAS mutation
• Peritonitis (secondary to perforation of the tumour) or symptomatic colonic occlusion or a temporary colostomy to prevent a sub-occlusion.
• Patient in whom an indication for radiotherapy exists based on the multidisciplinary meeting/board pre-operatively.
• Previous treatment with a BRAF inhibitor, cetuximab or other anti-EGFR treatment.
• History of acute or chronic pancreatitis within the 6 months prior to start of the study treatment.
• A history of chronic inflammatory bowel disease requiring treatment (with immuno-modulators or immuno-suppressants) ≤ 12 months before start of study treatment.
• Patient with decreased cardiovascular function or clinically significant cardiovascular disease:
• History of myocardial infarction, acute coronary syndrome (including unstable angina, coronary artery bypass grafting, coronary angioplasty or stent placement) ≤ 6 months prior to start of the study treatment.
• Symptomatic congestive heart failure (CHF) (grade 2 or higher), history or current evidence of cardiac arrhythmia and/or a clinically significant conduction disorder ≤ 6 months prior to start of the study treatment, except atrial fibrillation with controlled heart rate and paroxysmal supra-ventricular tachycardia.
• Child-Pugh class B or C cirrhosis.
• Deterioration of gastro-intestinal function or a disease which may significantly impair the absorption of encorafenib, e.g.: ulcer disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, small bowel resection
• A previous or concomitant malignant tumour within 5 years prior to the study. Except for basal cell or squamous skin cancer, superficial cancer of the bladder, intra-epithelial carcinoma of the prostate, carcinoma in situ of the uterine cervix or any other malignant tumour which has been treated adequately and which has not recurred during the three years prior to entry in the study.
• A concomitant neuro-muscular disease associated with high levels of creatinine kinase (CK).

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead
• Pierre Fabre Laboratories: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Chu - Hôpital Européen Georges Pompidou

Paris, France

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

encorafenib; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Claire Gallois, MD

  Paris HEGP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Project Manager

CONTACT

0033380393483; ffcd2006.neoraf@ffcd.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 31, 2023
• Study Start: February 13, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): May 31, 2029
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)