Study and Modulation of Immune Responses in Primary and Metastatic Colon Cancers

Colon Cancer Clinical Trial

— I-COMET  

Official title:

Etude et Modulation de la réponse Immunitaire Dans Les Cancers COlorectaux Primaires et METastatiques

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06435689
• Other study ID #: APHP231721
• Status: Not yet recruiting
• Start date: June 15, 2024
• Est. completion date: June 15, 2039

Study information

• Verified date: May 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Thomas Aparicio, Pr
• Phone: 142499597
• Email: thomas.aparicio[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Colorectal cancer (CRC) is the 3rd most common cancer in France. Treatment of CRC relies primarily on surgical removal of the primary tumor and chemotherapy is the current standard of care for synchronous metastatic disease. Overall survival remains strongly correlated with the tumor stage at the time of surgery, from 90% at five years for localized disease (stages 1 and 2), to around 20% for metastatic forms of the disease (stage 4). Recent research in cancer highlights the role of the immune system in the development, evolution and fate of tumors. Understanding the nature of interactions between different immune cells infiltrating the tumor is important for the development of innovative therapies. Recently, the consensus molecular classification of CRC confirmed the importance of the immune response in CRC by showing that a "high immune response" is a good prognostic indicator for patients with this pathology. However, immunotherapies are effective for only a minority of patients with metastatic CRC. Indeed, anti Programmed cell Death 1 (anti-PD-1), -PD-L1 immune checkpoint blocking antibodies have only shown effectiveness in patients with microsatellite instability (MSI), which only represents 5% of metastatic CRCs. Thus, the aim of this study is to better understand the role of the immune system on the development of CRC and its possible modulation to treat or prevent metastatic recurrences.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: June 15, 2039
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female 18 years of age or older
• Diagnosis of colorectal adenocarcinoma
• Scheduled resection of tumor and/or metastasis(es)

Exclusion Criteria:

• Patient's opposition to research
• Patients under guardianship
• The following situations

1. Persons unable to understand and/or read the information leaflet

2. Patient with one of the following functions: Investigator or co-investigator, research assistant, pharmacist, study coordinator or, having any involvement in the study

3. Non-cooperative or potentially non-compliant person for the study and its procedures with foreseeable difficulties in regular follow-up over 5 years.

4. Non-affiliation with a social security scheme, Couverture Médicale Universelle or any equivalent scheme.

• Pregnant or breast-feeding women.
• HIV-positive patients.

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms
• Peritoneal Carcinoma

Intervention

Other:
• Sampling
Blood and surgical specimen sampling the day of surgery

Locations

Country	Name	City	State
France	Hôpital Saint Louis - gastoenterology	Paris
France	Hôpital Saint Louis - visceral, oncological and endocrine surgery	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effectiveness of immunotherapies in a co-culture model	Characterize effective immunotherapies in colorectal cancers by demonstrating their effectiveness in a co-culture model between cancer cells and autologous T cells.	At 1 year
Secondary	Evaluation of transcriptomic differences	Evaluation of transcriptomic differences between tissues or cells from the healthy mucosa compared to those from the primary or metastatic tumor: sequencing of mRNA in the two types of mucosa and comparison of mRNA expression profiles between the latter.	At 5 years
Secondary	Evaluation of proteomic differences	Evaluation of proteomic differences between tissues or cells from the healthy mucosa in comparison to those from the primary tumor by: multiplexed immunodetection in situ in tissues detection and dosage of proteins in culture supernatants (ELISA), in a co-culture model between cancer cells and autologous T cells, with or without modulation of a pathway targeting the T lymphocyte response by immunotherapy.	At 5 years
Secondary	Evaluation of the T Cell Receptor (TCR) repertoire	Evaluation of the TCR repertoire by sequencing, carried out from: patient blood, DNA from cancerous tissues and healthy mucosa DNA from the co-culture between cancer cells and autologous T cells, with or without modulation of a pathway targeting the T lymphocyte response by immunotherapy	At 5 years