Prospective Cohort Study of Immunotherapy Resistance in Metastatic Colorectal Cancer Patients With MSI

Colorectal Cancer Metastatic Clinical Trial

— CORESIM  

Official title:

Prospective National Cohort Study of Factors Predictive of Immunotherapy Resistance in Metastatic Colorectal Cancer Patients With Microsatellite Instability

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: April 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

Over the last ten years, the discovery of the mechanisms by which tumours escape the control of the immune system, and in particular the T lymphocyte response, has led to the emergence of new therapeutic strategies against cancer, such as the use of "immune checkpoint inhibitors" (ICI). The immune system plays a crucial role in controlling tumour proliferation, and involves several players. Schematically, after recognition of the MHC-peptide complex by the TCR, the T lymphocyte response is modulated by several activating or inhibiting co-stimulatory signals (or "checkpoints"). The balance of these different signals determines whether the T lymphocyte (LT) is activated, resulting in the destruction of the target cell, or whether the T lymphocyte is inhibited (anergy), inducing immune tolerance. By hijacking this system through the expression of inhibitory checkpoints on its surface, the tumour cell is able to evade the effector immune response (1). Monoclonal antibodies (mAbs) directed against inhibitory co-stimulatory molecules such as Programmed-cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) or their ligand Programmed-cell death ligand 1 (PD-L1) have been developed to restore effective anti-tumour immunity. These ICIs have led to a major improvement in the prognosis of certain cancers, notably melanoma and non-small cell lung cancer. However, the efficacy of ICIs varies from one cancer to another. In addition to the expression of PDL1 by the tumour and/or immune cells, and the mutational load, one of the primary factors predicting response to immunotherapy mentioned in several studies is microsatellite instability (MSI).

Description:

In order to meet our objectives, we plan to construct a retrospective and prospective, multicentre cohort. National recruitment will be carried out in all French centres, including the FFCD, AGEO, GERCOR, and UNICANCER, representing more than 150 centres and the majority of French sites, public and private hospitals. A total of 600 patients are expected. Some will be included retrospectively over the last two years prior to the launch of the prospective cohort. 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:

• Histologically confirmed colorectal adenocarcinoma with unresectable metastasis(s) receiving first-line immunotherapy with pembrolizumab
• Tumour 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 tumour DNA according to the standard practice of the donor centre). (= indication for pembrolizumab according to the marketing authorisation).

Exclusion Criteria:

• Patients with another concomitant cancer at the time of diagnosis requiring systemic treatment or influencing prognosis according to the medical team.
• Previous treatment with anti-PD1 or anti-PDL1.
• Previous treatment with chemotherapy +/- targeted therapy for metastatic colorectal cancer MSI/dMMR
• Contraindication due to psychological or socio-demographic reasons that may hinder follow-up (cognitive deficit, psychological disorders incompatible with obtaining non-opposition or consent; inability to be followed in the same centre throughout the follow-up period for geographical reasons).
• Pregnant women and people under court protection
• Patient under protective supervision (guardianship or curators)
• 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 immunotherapy in first-line treatment of unresectable mRCC	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