## Protocol Section
### Identification Module
**NCT ID:** NCT06435689

**Acronym:** I-COMET

**Brief Title:** Study and Modulation of Immune Responses in Primary and Metastatic Colon Cancers

**Official Title:** Etude et Modulation de la réponse Immunitaire Dans Les Cancers COlorectaux Primaires et METastatiques

#### Organization Study ID Info
**ID:** APHP231721
#### Organization
**Class:** OTHER
**Full Name:** Assistance Publique - Hôpitaux de Paris
### Status Module
#### Completion Date
**Date:** 2039-06-15

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-26

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-06-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-15

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-26
**Study First Submit QC Date:** 2024-05-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Assistance Publique - Hôpitaux de Paris

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief 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.

### Conditions Module

**Conditions:**

- Colon Cancer

- Peritoneal Carcinoma

**Keywords:**

- Organoids

- T-cells

- Metastasis

- Immunotherapies

### Design Module

#### Bio Spec

**Description:** Blood and surgical specimen sampling the day of surgery (primary tumor and metastases if applicable)

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 500

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Other: Sampling

**Label:** Patients undergoing surgery for the treatment of primary and/or metastatic colorectal cancers

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Patients undergoing surgery for the treatment of primary and/or metastatic colorectal cancers

**Description:** Blood and surgical specimen sampling the day of surgery

**Name:** Sampling

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Characterize effective immunotherapies in colorectal cancers by demonstrating their effectiveness in a co-culture model between cancer cells and autologous T cells.

**Measure:** Effectiveness of immunotherapies in a co-culture model

**Time Frame:** At 1 year

#### Secondary Outcomes

**Description:** 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.

**Measure:** Evaluation of transcriptomic differences

**Time Frame:** At 5 years

**Description:** 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.

**Measure:** Evaluation of proteomic differences

**Time Frame:** At 5 years

**Description:** 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

**Measure:** Evaluation of the T Cell Receptor (TCR) repertoire

**Time Frame:** At 5 years

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Patients undergoing surgery for the treatment of primary and/or metastatic colorectal cancers

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** thomas.aparicio@aphp.fr

**Name:** Thomas Aparicio, Pr

**Phone:** 142499597

**Phone Ext:** +33

**Role:** CONTACT

**Contact 2:**

**Email:** jerome.lambert@u-paris.fr

**Name:** Jérôme Lambert, Pr

**Phone:** 142499742

**Phone Ext:** +33

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Email:** thomas.aparicio@aphp.fr

- **Name:** Thomas Aparicio, Pr

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Saint Louis - gastoenterology

**Location 2:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Email:** diane.goere@aphp.fr

- **Name:** Diane Goéré, Pr

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Saint Louis - visceral, oncological and endocrine surgery

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000015179

- Term: Colorectal Neoplasms

- ID: D000007414

- Term: Intestinal Neoplasms

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M6338

- Name: Colonic Neoplasms

- Relevance: HIGH

- As Found: Colon Cancer

- ID: M17890

- Name: Colorectal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M10448

- Name: Intestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003110

- Term: Colonic Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: HB

- Name: Herbal and Botanical

### Intervention Browse Module - Browse Leaves

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: T120

- Name: Cola

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
