Prospective National Cohort Evaluating Predictive Biomarkers of Resistance to Immunotherapy in Patients With MSI/dMMR Metastatic Colorectal Cancer (CORESIM)

Colorectal Cancer Metastatic Clinical Trial

— CORESIM  

Official title:

National French Cohort Evaluating Predictive Factors of Resistance to Immunotherapy in Patients With MSI Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06353854
• Other study ID #: FFCD 2112-CORESIM
• Status: Recruiting
• Start date: February 12, 2024
• Est. completion date: February 12, 2030

Study information

• Verified date: June 2024
• Source: Federation Francophone de Cancerologie Digestive
• Contact: Aziz ZAANAN, MD, PhD
• Phone: 03 80 66 80 13
• Email: aziz.zaanan[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The Keynote 117 phase III trial demonstrated the superiority of pembrolizumab (anti-PD1 monoclonal antibody) versus chemotherapy +/- targeted therapy in first-line treatment of dMMR/MSI metastatic colorectal cancer (mCRC). However, primary resistance to pembrolizumab was observed in approximately 20-30% of patients treated in the Keynote 177 study. Therefore, the identification of biomarkers predictive of resistance to immunotherapy for dMMR/MSI mCRC is necessary to better select patients who benefit the most from immunotherapy, and those for whom other therapeutic approaches should be favored.

Description:

The primary endpoint is the identification of predictive factors of resistance to pembrolizumab in first-line treatment of MSI and/or dMMR metastatic colorectal cancer

CORESIM is a retrospective and prospective multicenter national French cohort. National recruitment will be carried out in all French centers, including the FFCD, AGEO, GERCOR, and UNICANCER, representing more than 150 centers and most French sites, public and private hospitals.

In France, pembrolizumab for first-line treatment of patients with MSI mCRC was accessible via its compassionate use in February 2021, then its reimbursement was effective in June 2023 Patients treated with pembrolizumab will be included prospectively on the start date of the study, i.e. on February 2024; patients treated since February 2021 via compassionate use of pembrolizumab will be included retrospectively A total of 600 patients are expected. The theoretical duration of inclusion is set at 2 years. All patients will be followed up for 3 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: February 12, 2030
• Est. primary completion date: February 12, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients over 18 years old

• Histologically confirmed colorectal adenocarcinoma with unresectable metastasis(s) receiving immunotherapy as first-line treatment with pembrolizumab

• Tumor with microsatellite instability determined by immunohistochemistry (loss of expression of MLH1, MSH2, MSH6 and/or PMS2) and/or by molecular biology (MSI-H on microsatellite analysis from tumor DNA according to practice routine of the center)

Exclusion Criteria:

• Patients with another concomitant cancer at the time of diagnosis requiring systemic treatment or impacting prognosis according to the medical team.

• Previous treatment with anti-PD1 or anti-PDL1.

• Previous treatment with chemotherapy +/- targeted therapy for MSI/dMMR metastatic colorectal cancer.

• Contraindication due to psychological or social reasons that may hinder follow-up (cognitive deficit, psychological disorders incompatible with obtaining non-opposition or consent; inability to be followed in the same center throughout the follow-up period for geographical reasons).

• Pregnant women

• persons under court protection or under protective supervision (guardianship or curatorship)

• Opposition to participation in the study.

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Microsatellite Instability

Locations

Country	Name	City	State
France	Ch - Centre Hospitalier de La Côte Basque	Bayonne CEDEX
France	Ch - Ch Beauvais	Beauvais
France	CH Jean Minjoz	Besançon
France	Polyclinique Saint Privat	Boujan-sur-Libron
France	Ch - Duchenne	Boulogne-sur-Mer
France	Ch - Centre Hospitalier Metropole Savoie	Chambéry CEDEX
France	Ch - Centre Hospitalier de Cholet	Cholet
France	CH - Compiegne	Compiègne
France	Ch - Chd Vendée	La Roche-sur-Yon
France	CH - Louis Pasteur	Le Coudray
France	Centre Hospitalier Regional et Universitaire de Lille	Lille
France	Caluire et Cuire - Infirmerie Protestante de Lyon	Lyon
France	CH Saint Joseph - Saint Luc	Lyon
France	Ch - Hôpital Saint Joseph	Marseille
France	CH Saint Joseph	Marseille
France	Centre Hospitalier	Mulhouse
France	CHR D'Orleans - Hopital de la Source	Orleans
France	Prive - Institut Montsouris	Paris
France	Ch - Centre Hospitalier de Soisson	Soissons CEDEX
France	CH - Gustave Dron	Tourcoing

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of predictive factors of resistance to pembrolizumab in first-line treatment of MSI and/or dMMR metastatic colorectal cancer	Primary resistance will be defined as immediate progression of the disease (at the time of the first assessment, excluding pseudoprogression) Secondary resistance will be defined as progression occurring after control of the disease.	2 years