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

Metastatic Colorectal Cancer Clinical Trial

— COBRAF  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05639413
• Other study ID #: UC-GIG-2210/PRODIGE75
• Secondary ID: 2022-A02232-41
• Status: Recruiting
• Phase: N/A
• Start date: July 24, 2023
• Est. completion date: July 2028

Study information

• Verified date: November 2023
• Source: UNICANCER
• Contact: Emilie BRUMENT
• Phone: +33(0)1 71 93 61 64
• Email: e-brument[@]unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: July 2028
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• BRAF V600E Mutation Positive
• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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.

Locations

Country	Name	City	State
France	Centre Hospitalier D'Avignon	Avignon
France	Centre Hospitalier de Bayeux	Bayeux
France	Institut Bergonie	Bordeaux
France	Ch de Cahors	Cahors
France	Infirmerie Protestante de Lyon	Caluire-et-Cuire
France	Chu Estaing de Clermont-Ferrand	Clermont-Ferrand
France	Aphp - Hopital Henri Mondor	Créteil
France	Groupe Hospitalier Mutualiste de Grenoble	Grenoble
France	Chu de Grenoble Alpes - Hopital Michallon	La Tronche
France	Groupe Hospitalier Emile Roux	Le Puy-en-Velay
France	Hopital Franco-Britannique	Levallois-Perret
France	Chu Dupuytren	Limoges
France	Centre Leon Berard	Lyon
France	Intitut Paoli Calmettes	Marseille
France	Grand Hopital de L'Est Francilien - Site de Meaux	Meaux
France	Centre Antoine Lacassagne	Nice
France	Aphp - Hopital Bichat	Paris
France	Aphp - Hopital Saint Louis	Paris
France	Aphp - La Pitie Salpetriere	Paris
France	Gh Diaconesses Croix Saint Simon	Paris
France	Hopital Saint Antoine	Paris
France	Institut Mutualiste Montsouris	Paris
France	Ch Perpignan	Perpignan
France	Chu Poitiers	Poitiers
France	Chu de Reims	Reims
France	Chu Rennes Pontchaillou	Rennes
France	Chu de Rouen	Rouen
France	Ch de Saint Malo	Saint-Malo
France	ICANS	Strasbourg
France	Chu de Tours	Tours
France	Chru de Nancy	Vandœuvre-lès-Nancy

Sponsors (2)

Lead Sponsor	Collaborator
UNICANCER	Pierre Fabre Medicament

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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	Collection of prospective data about BRAFV600E mCRC	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
Secondary	Correlation between prognostic markers and progression-free survival	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
Secondary	Correlation between prognostic markers and overall survival	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
Secondary	Objective response rate	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
Secondary	Disease control rate	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
Secondary	Progression-free survival	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
Secondary	ctDNA kinetics modeling outcome parameters	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
Secondary	Correlation between predictive biomarkers and response to treatment	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