Colorectal CancerPhase 2NEORAFNCT05706779
Encorafenib Plus Cetuximab in a Neoadjuvant Setting in Patients With BRAF Mutation Localised Colon or Upper Rectum Cancer
A Phase 2 study testing Encorafenib Oral Capsule + Cetuximab in people with Colorectal Cancer and BRAF V600E Mutation Positive, run by Federation Francophone de Cancerologie Digestive at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, BRAF V600E Mutation Positive
- What is being tested?
- Encorafenib Oral Capsule + Cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 13 Feb 2023to 31 May 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
- Total serum bilirubin ≤ 25 μmol/L, ALT and/or AST ≤ 2.5 x ULN.
- Cardiac function considered satisfactory:
- o Corrected mean QT interval for heart rate according to the Fridericia formula (QTcF) ≤ 480 ms.
- Patient able to take medicinal products by mouth (OD).
- Female Patients postmenopausal for at least one year or surgically infertile for at least 6 weeks, or effective contraception for male and female patients of childbearing potential for 2 months after the end of the investigational treatments
- A negative pregnancy test for inclusion for all female patients of child-bearing FFCD 2006 - NEORAF Version 1.0- 21/October2022 Page 7 of 69 potential.
- Patient covered by a plan of the French Social Security system
Who cannot join
- 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.
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- 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).
- Remark: inflammatory muscular disease, muscular dystrophy, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy.
- History of infection with human immunodeficiency virus (HIV).
- Active infection with hepatitis B or hepatitis C.
- Known existence of Gilbert syndrome
- Use of medicinal plants/dietary supplements or other medicinal products or foods that are potent inducing agents or inhibitors of cytochrome P450 (CYP) 3A4/5 ≤ 1 week before start of the study treatment.
- Known severe hypersensitivity reactions to monoclonal antibodies or BRAF-inhibitors (grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
- Participation in a clinical study with administration of an investigational product within 4 weeks or five times the half-life of the investigational product, according to the longest period, prior to the first dose of the study treatment.
- Persons who are deprived of their freedom or who are under guardianship
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Chu - Hôpital Européen Georges Pompidou
Paris
Claire GALLOIS, Dr, 0156092297, claire.gallois@aphp.fr
Claire GALLOIS, Dr
About this study
Official title: Combination of Encorafenib Plus Cetuximab in a Neoadjuvant Setting in Patients With Braf v600e-mutates Localised Colon or Upper Rectum Cancer (Neoraf Study)
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
- Being tested
- Encorafenib Oral Capsule + Cetuximab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Encorafenib Oral Capsule + CetuximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Encorafenib + Cetuximab | Experimental | Not described Receives: Drug: Encorafenib Oral Capsule + Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months after completing inclusions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2023
- Study start13 Feb 2023
- Primary completion30 Dec 2026 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federation Francophone de Cancerologie Digestive
- Sponsor type
- University, hospital or other
- Collaborators
- Pierre Fabre Laboratories, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Claire Gallois, MD, Principal investigator, Paris HEGP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05706779
- Sponsor's protocol ID
- FFCD 2006 NEORAF
- Acronym
- NEORAF
- Status last verified
- Aug 2025
- First submitted
- 20 Jan 2023
- Last updated
- 2 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination of Encorafenib Plus Cetuximab in a Neoadjuvant Setting in Patients With Braf v600e-mutates Localised Colon or Upper Rectum Cancer (Neoraf Study)
- ClinicalTrials.gov ID
- NCT05706779
- Acronym / sponsor ID
- NEORAF / FFCD 2006 NEORAF
- Conditions
- Colorectal Cancer, BRAF V600E Mutation Positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Federation Francophone de Cancerologie DigestiveUniversity, hospital or other
- Collaborators
- Pierre Fabre Laboratories, Merck Sharp & Dohme LLC
- Study start
- 13 Feb 2023 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 31 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Encorafenib + Cetuximab | Experimental | Drug: Encorafenib Oral Capsule + Cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Encorafenib Oral Capsule + CetuximabEncorafenib: 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. | Drug | Encorafenib + Cetuximab |
Primary outcome
To assess the rate of significant tumour regression (TRG 0 to 2 according to Ryan's modified score of the AJCC 2010)
Time frame: 6 months after completing inclusions
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Claire Gallois, MD principal investigator
Paris HEGP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Encorafenib Oral Capsule + Cetuximab in people with Colorectal Cancer and BRAF V600E Mutation Positive, run by Federation Francophone de Cancerologie Digestive at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Project Manager (0033380393483, ffcd2006.neoraf@ffcd.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the rate of significant tumour regression (TRG 0 to 2 according to Ryan's modified score of the AJCC 2010) (time frame: 6 months after completing inclusions). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.