A Clinical-biological Prospective Cohort of Patients With BRAFV600E-mutated Metastatic Colorectal Cancer (COBRAF)

December 9, 2025 updated by: UNICANCER

A Study to Collect Patients, Medical, and Biological Data From Patients Being Treated for Metastatic Colorectal Cancer With a Specific Genetic Mutation: BRAFV600E

The study will be conducted in patients with metastatic colorectal cancer (mCRC) harboring a BRAFV600E mutation, to collect clinical data and biological samples to be used for research but also to gather real-world clinical data concerning the treatments and the survival outcomes in patients with this pathology.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Despite substantial progress made in the first- and second line mCRC settings, there are still unmet clinical needs for patients harboring BRAFV600E mutations, especially those with microsatellite stability (MSS) / proficient mismatch repair (pMMR) tumor. The overall survival and access to different treatment in the real-life setting are unknown. Moreover, patient prognosis remains poor and therapeutic resistance to combinations with BRAF inhibitors, is at present, nearly universal. Therefore, it seems essential to prospectively collect clinical and biological data about this rare mCRC subtype. These data will allow us to improve knowledge and to identify clinical and biological factors that could drive therapeutic decisions, predict resistance to treatments, and that are prognostic for survival. In this context, we designed this large, prospective, cohort study to collect clinical data and biological samples to be used for research but also to gather real-world clinical data concerning the treatments and the survival outcomes in patients with BRAFV600E mCRC.

This collection of clinical and biological data (tumor tissue and blood samples) will allow us to identify predictive and prognostic biomarkers with several research work packages planned:

i. To evaluate the circulating tumor DNA (ctDNA) during the metastatic first-, second-, and third-line treatment to:

  • Evaluate its positive and negative predictive value.
  • Identify molecular alterations preceding and explaining clinical resistance during BRAF/EGFR inhibition therapy and immunotherapy.

ii. To evaluate BRAFV600E mCRC immune environment both at the tumor and blood level (immunomonitoring).

iii. To study specific the dMMR/MSI BRAFV600E subgroup. Furthermore, the data collected will describe the therapeutic management of BRAFV600E mCRC patients in the routine-practice setting which will bring very useful data. The results of the COBRAF study could lay the groundwork to better understand BRAFV600E mCRC and to identify prognostic and predictive biomarkers helping the development of new therapeutic approaches in this population.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Avignon, France, 84000
        • Active, not recruiting
        • Centre hospitalier d'Avignon
      • Bayeux, France, 14400
        • Recruiting
        • Centre Hospitalier de Bayeux
        • Contact:
      • Beauvais, France
        • Active, not recruiting
        • Chu Simone Veil
      • Bordeaux, France, 33076
      • Bourg-en-Bresse, France, 01000
        • Active, not recruiting
        • CH Fleyriat
      • Cahors, France
      • Calais, France, 62107
        • Active, not recruiting
        • CH Dr TECHER
      • Caluire-et-Cuire, France
        • Active, not recruiting
        • Infirmerie Protestante de Lyon
      • Clermont-Ferrand, France, 63003
      • Creil, France
        • Recruiting
        • GHPSO
        • Contact:
          • Elisabeth CAROLA, MD
      • Créteil, France
      • Grenoble, France, 38028
        • Withdrawn
        • Groupe hospitalier mutualiste de Grenoble
      • La Tronche, France, 38700
        • Withdrawn
        • CHU de Grenoble Alpes - Hôpital Michallon
      • Le Coudray, France, 28630
        • Not yet recruiting
        • CH Louis Pasteur
        • Contact:
          • David SOLUB, MD
      • Le Puy-en-Velay, France
      • Levallois-Perret, France, 92300
        • Active, not recruiting
        • Hôpital Franco-Britannique
      • Limoges, France, 87042
      • Lyon, France, 69008
      • Lyon, France, 69373
        • Active, not recruiting
        • Hopital Prive Jean Mermoz
      • Marseille, France
        • Not yet recruiting
        • Hopital De La Timone
        • Contact:
          • Laétitia DAHAN, MD
      • Marseille, France
      • Meaux, France
        • Active, not recruiting
        • Grand Hopital de L'Est Francilien - Site de Meaux
      • Nice, France
      • Orléans, France, 45100
        • Active, not recruiting
        • CHR d'Orléans
      • Paris, France
        • Recruiting
        • Hôpital Européen Georges Pompidou
        • Contact:
          • Claire GALLOIS, MD
      • Paris, France, 75012
        • Recruiting
        • Hôpital Saint Antoine
        • Contact:
      • Paris, France, 75014
        • Recruiting
        • Institut Mutualiste Montsouris
        • Contact:
      • Paris, France, 75010
        • Recruiting
        • APHP - Hôpital Saint Louis
        • Contact:
      • Paris, France, 75013
        • Recruiting
        • APHP - Hôpital BICHAT
        • Contact:
      • Paris, France, 75013
        • Recruiting
        • APHP - La Pitié Salpétrière
        • Contact:
      • Paris, France, 75020
        • Recruiting
        • GH Diaconesses Croix Saint Simon
        • Contact:
      • Perpignan, France
      • Poitiers, France, 86021
      • Reims, France, 51100
        • Recruiting
        • CHU de Reims
        • Contact:
      • Rennes, France, 35000
      • Rouen, France, 76031
      • Saint-Etienne, France, 42100
        • Active, not recruiting
        • Hôpital Privé de la Loire
      • Saint-Mandé, France
        • Active, not recruiting
        • Hnia Begin
      • St-Malo, France
        • Active, not recruiting
        • CH de Saint Malo
      • Strasbourg, France, 67033
        • Recruiting
        • Centre Paul Strauss
        • Contact:
      • Toulon, France
        • Not yet recruiting
        • Hnia Saint Anne
        • Contact:
          • Caroline PRIEUX-KLOTZ, MD
      • Tours, France, 37044
        • Recruiting
        • CHU de Tours
        • Contact:
      • Vandœuvre-lès-Nancy, France
        • Not yet recruiting
        • Institut de Cancérologie de Lorraine
        • Contact:
          • Edwige BAUDRY, MD
      • Vandœuvre-lès-Nancy, France, 54500
      • Vannes, France, 56000
        • Recruiting
        • Centre d'oncologie Saint Yves
        • Contact:
          • Valentine DISDERO, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Men and women aged 18 years or older
  2. Histologically confirmed BRAFV600E metastatic colorectal cancer (mCRC), chemotherapy-naive in the metastatic setting or having initiated a first line of chemotherapy in the metastatic setting (except encorafenib-cetuximab treatment)
  3. Available tumor tissue sample obtained before inclusion with sufficient tissue left for biological studies. Patients with only fine-needle aspirations are not eligible.
  4. Known MMR/microsatellite status (immunohistochemistry [IHC] and polymerase chain reaction [PCR]) (or under analysis)
  5. Patients must have signed a written informed consent form prior to any trial specific procedures. If the patients are physically unable to give their written consent, a trusted person of their choice, not related to the investigator or the sponsor, can confirm in writing the patient's consent.
  6. Patients must be willing and able to comply with the study procedures
  7. The patient must be affiliated to a social security system or benefit of such a system.

Exclusion Criteria:

  1. Patient with another cancer concomitantly with the mCRC requiring treatment or influencing the prognosis according to the medical staff.
  2. Patients for whom the follow-up will not be assured by the investigator or its team.
  3. Any condition that may jeopardize patient participation in the study as well as non-contraception for men and women with child-bearing potential, and pregnancy or breast feeding for women.
  4. Persons deprived of their liberty or under protective custody or guardianship.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: COBRAF

A 30 mL blood samples (6 mL in each of 5 EDTA tubes) will be collected from each patient at the following timepoints:

  • At the starts of cycle 1, 2 and 3,
  • At 3 and 6 months after starting of each treatment line, if applicable.
  • At disease progression after second-line treatment with encorafenib combined with cetuximab, if applicable.
  • At disease progression after immunotherapy-based treatment in dMMR/MSI patients.

At most 390 mL of blood will be collected from each patient during the study.
Other: Collection of blood samples
A 30 mL blood samples (6 mL in each of 5 EDTA tubes) will be collected from each patient at each timepoint.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From date of first diagnosis of mCRC and the date of death, whatever the cause, up to 5 years
OS of patients with BRAFV600E mCRC in the real-life setting. The OS is defined as the time between the date of first diagnosis of mCRC and the date of death, whatever the cause. The patients alive at the time of analysis will be censored at the date of their last follow up.
From date of first diagnosis of mCRC and the date of death, whatever the cause, up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Collection of prospective data about BRAFV600E mCRC
Time Frame: Throughout study completion, up to 5 years
Prospective collection of data collected during the normal clinical care. A descriptive analysis of the disease (Patients and tumors characteristics), current medical practices (molecular genotyping in France), and therapeutic sequences and composition of each treatment line (patients treated with immunotherapy, patients enrolled in clinical studies, metastatic surgeries). The resulting qualitative data analysis of the population will be expressed in number with percentage.
Throughout study completion, up to 5 years
Correlation between prognostic markers and progression-free survival
Time Frame: From date of first diagnosis of mCRC and date of first progression or death, up to 5 years
PFS is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. PFS will then be correlated to clinical and biological prognostic markers analyzed at date of first diagnosis of mCRC and date of first progression or death by clinical testing used in routine cancer treatment practice (blood test analysis and tumor sample analysis). The Cox proportional-hazards model will then be used to study potential prognostic parameters PFS.
From date of first diagnosis of mCRC and date of first progression or death, up to 5 years
Correlation between prognostic markers and overall survival
Time Frame: Throughout study completion, up to 5 years
To identify clinical and biological prognostic markers of OS on blood and tumor samples. the OS is defined as the length of time from first diagnosis of mCRC that patients enrolled in the study are still alive. OS will then be correlated to clinical and biological prognostic markers analyzed at date of first diagnosis of mCRC and date of first progression or death by clinical testing used in routine cancer treatment practice (blood test analysis and tumor sample analysis). The Cox proportional-hazards model will then be used to study potential prognostic parameters OS.
Throughout study completion, up to 5 years
Objective response rate
Time Frame: From baseline to first disease progression, up to 5 years
The objective response rate (ORR) for each treatment line is defined as the percentage of patients with a complete response (CR) or a partial response (PR) for a given treatment line.
From baseline to first disease progression, up to 5 years
Disease control rate
Time Frame: From baseline to first disease progression, up to 5 years
The disease control rate (DCR) is defined as the percentage of patients with a CR, a PR or stable disease for a given treatment line.
From baseline to first disease progression, up to 5 years
Progression-free survival
Time Frame: From baseline to first disease progression, up to 5 years
The progression-free survival (PFS) for each treatment line is defined as the time interval between the start of treatment of the given line and the date of the first disease progression (radiological or clinical) or the start of another anticancer therapy, or death from any cause, whichever occurs first.
From baseline to first disease progression, up to 5 years
ctDNA kinetics modeling outcome parameters
Time Frame: From date of first diagnosis of mCRC until the date of first disease progression, up to 5 years

The detection of ctDNA level assessed by next generation sequencing in the blood of patients with deficient DNA mismatch repair (dMMR) / microsatellite instability (MSI) will be measured at the start of cycle 1, cycle 2, and cycle 3, and at 3 months and 6 months after starting each treatment line, as well as at disease progression.

The level of ctDNA measured at each time point will provide information on how the body interacts with administered treatments overtime.
From date of first diagnosis of mCRC until the date of first disease progression, up to 5 years
Correlation between predictive biomarkers and response to treatment
Time Frame: Throughout study completion, up to 5 years
These biomarkers of response/resistance to combination treatment with anti-EGFR/anti-BRAF will be assessed by immunohistochemistry analysis of peripheral blood and tumor tissues.
Throughout study completion, up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNICANCER

Collaborators

Pierre Fabre Medicament

Investigators

  • Principal Investigator: Christelle DE LA FOUCHARDIERE, MD, Centre Léon Bérard - Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 24, 2023

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

November 15, 2022

First Submitted That Met QC Criteria

November 25, 2022

First Posted (Actual)

December 6, 2022

Study Record Updates

Last Update Posted (Actual)

December 10, 2025

Last Update Submitted That Met QC Criteria

December 9, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UC-GIG-2210/PRODIGE75
  • 2022-A02232-41 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

IPD Sharing Time Frame

Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

IPD Sharing Access Criteria

The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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