Clinical trial NCT05639413: A Clinical-biological Prospective Cohort of Patients With BRAFV600E-mutated Metastatic Colorectal Cancer
Official title: A Study to Collect Patients, Medical, and Biological Data From Patients Being Treated for Metastatic Colorectal Cancer With a Specific Genetic Mutation: BRAFV600E
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Metastatic Colorectal Cancer
BRAF V600E Mutation Positive
Keywords: Clinical-biological cohort
Colorectal Cancer
BRAF mutation
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Pierre Fabre Medicament
First posted: 2022-12-06
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The COBRAF study was designed as a prospective, multicenter, study. The study is without a therapeutic intervention and is of minimal risk and constraints (category 2 according to the "Loi Jardé"). The study will be conducted in patients with mCRC harboring a BRAFV600E mutation.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of first diagnosis of mCRC and the date of death, whatever the cause, up to 5 years
Secondary outcomes:
measure: Collection of prospective data about BRAFV600E mCRC
timeFrame: Throughout study completion, up to 5 years
measure: Correlation between prognostic markers and progression-free survival
timeFrame: From date of first diagnosis of mCRC and date of first progression or death, up to 5 years
measure: Correlation between prognostic markers and overall survival
timeFrame: Throughout study completion, up to 5 years
measure: Objective response rate
timeFrame: From baseline to first disease progression, up to 5 years
measure: Disease control rate
timeFrame: From baseline to first disease progression, up to 5 years
measure: Progression-free survival
timeFrame: From baseline to first disease progression, up to 5 years
measure: ctDNA kinetics modeling outcome parameters
timeFrame: From date of first diagnosis of mCRC until the date of first disease progression, up to 5 years
measure: Correlation between predictive biomarkers and response to treatment
timeFrame: Throughout study completion, up to 5 years
Other outcomes:
Locations:
city: Avignon
country: France
facility: Centre Hospitalier D'Avignon
city: Bayeux
country: France
facility: Centre Hospitalier de Bayeux
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bourg-en-Bresse
country: France
facility: CH Fleyriat
city: Cahors
country: France
facility: Ch de Cahors
city: Calais
country: France
facility: CH Dr TECHER
city: Caluire-et-Cuire
country: France
facility: Infirmerie Protestante de Lyon
city: Clermont-Ferrand
country: France
facility: Chu Estaing de Clermont-Ferrand
city: Créteil
country: France
facility: Aphp - Hopital Henri Mondor
city: Grenoble
country: France
facility: Groupe Hospitalier Mutualiste de Grenoble
city: La Tronche
country: France
facility: Chu de Grenoble Alpes - Hopital Michallon
city: Le Coudray
country: France
facility: CH Louis Pasteur
city: Le Puy-en-Velay
country: France
facility: Groupe Hospitalier Emile Roux
city: Levallois-Perret
country: France
facility: Hopital Franco-Britannique
city: Limoges
country: France
facility: Chu Dupuytren
city: Lyon
country: France
facility: Centre Leon Berard
city: Lyon
country: France
facility: Hôpital privé Jean Mermoz
city: Marseille
country: France
facility: Intitut Paoli Calmettes
city: Meaux
country: France
facility: Grand Hopital de L'Est Francilien - Site de Meaux
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: Aphp - Hopital Saint Louis
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Aphp - Hopital Bichat
city: Paris
country: France
facility: Aphp - La Pitie Salpetriere
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Gh Diaconesses Croix Saint Simon
city: Perpignan
country: France
facility: Ch Perpignan
city: Poitiers
country: France
facility: Chu Poitiers
city: Reims
country: France
facility: Chu de Reims
city: Rennes
country: France
facility: Chu Rennes Pontchaillou
city: Rouen
country: France
facility: Chu de Rouen
city: Saint Etienne
country: France
facility: Hôpital Privé de la Loire
city: Saint-Malo
country: France
facility: Ch de Saint Malo
city: Strasbourg
country: France
facility: ICANS
city: Tours
country: France
facility: Chu de Tours
city: Vandœuvre-lès-Nancy
country: France
facility: Chru de Nancy
city: Vannes
country: France
facility: Centre d'Oncologie Saint Yves
Study officials:
affiliation: CENTRE LEON BERARD - LYON
name: Christelle DE LA FOUCHARDIERE, MD
role: PRINCIPAL_INVESTIGATOR
References: