Interaction Between Host, Microenvironment and Immunity on Gastrointestinal Neoplasms

NCT ID: NCT04363983

Last Updated: 2022-02-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

6300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-13

Study Completion Date

2031-01-31

Brief Summary

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The primary objective: association study of characteristics of tumoral microenvironment and immunity of digestive cancers with patients' overall survival (OS).

Detailed Description

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The study aims to explore relationship between the molecular subgroups (DNA and RNA analysis), tumor microenvironment, host (immunity system, premetastatic niche, microbiota, metabolism) and survival (prognostic value), response (predictive value) and tolerance (toxicities) to conventional treatments or immunotherapies in digestive cancers, in particular, in colorectal cancer and pancreaticobiliary cancer.

This is a prognostic monocentric study which includes 2 parts:

* one retrospective observational cohort for which 150 eligible patients (who have being diagnosed between 1998 to 2020) will be entered in the cohort per year during 22 years targeting 3300 patients and
* one prospective interventional cohort in which 3000 patients (diagnosis will be done between 2020-2030) will be enrolled during 10 years. 10 years of follow-up for all patients. This cohort is non comparative, non randomized, non control.

The enrollment will last 10 years in Digestive Surgery Department, Ambroise Paré Hospital, APHP.

There is any change in management of patients' care who will participate to the study, all of the treatment modalities (i.e. surgery, chemotherapy, radiotherapy, immunotherapy, intra-arterial treatments and supportive care) are possible and choice of treatment will be made by investigator physician, after multidisciplinary meeting validation, and according to referential and recommendations of practice in department.

Statistic analysis

The statistic analysis will be performed and reported according to the international guidelines STROBE for the observational studies.

Conditions

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Gastrointestinal Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Located/resected colorectal cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Liver biopsy

Intervention Type PROCEDURE

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Advanced colorectal cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Located/resected pancreatic cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Liver biopsy

Intervention Type PROCEDURE

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Advanced pancreatic cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Located/resected biliary tract cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Liver biopsy

Intervention Type PROCEDURE

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Advanced biliary tract cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Located/resected gastroesophageal cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Liver biopsy

Intervention Type PROCEDURE

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Advanced gastroesophageal cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Located/resected neuroendocrine cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Liver biopsy

Intervention Type PROCEDURE

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Advanced neuroendocrine cancer

Group Type ACTIVE_COMPARATOR

Blood sampling

Intervention Type BIOLOGICAL

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Stool collect

Intervention Type BIOLOGICAL

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Interventions

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Blood sampling

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,…; methylation) and circulating tumor cells.

Intervention Type BIOLOGICAL

Liver biopsy

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Intervention Type PROCEDURE

Stool collect

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Carcinoma of colorectal, pancreatic, biliary tract or gastro-oesophageal, or neuroendocrine digestive tumors with cytologically or histologically proven, regardless of the stage;
* Diagnosis between 1998 and 2030;
* Be \>/= 18 years;
* Have obtained signed informed consent (exemption for dead patients);
* Affiliated to the French social security - welfare system in France (CMU included).

Exclusion Criteria

* Patient under tutoraship or curatorship;
* Foreign patient under AME schema, a medical help from the state in France;
* Pregnant or breastfeeding women (for prospective study);
* Any clinical, psychological or social reason which should influence patient compliance with protocol, according to investigator;
* Patient refusal.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frédérique PESCHAUD, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Digestive Surgery Department, Ambroise Paré Hospital, APHP

Cindy NEUZILLET, MD

Role: STUDY_DIRECTOR

Digestive Surgery Department, Ambroise Paré Hospital, APHP

Locations

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Digestive Surgery Department, Ambroise Paré Hospital, APHP

Boulogne-Billancourt, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Frédérique PESCHAUD, MD, PhD

Role: CONTACT

+33 1 49 09 53 35

Cindy NEUZILLET, MD

Role: CONTACT

+33 1 47 11 15 15

Other Identifiers

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2019-A03330-57

Identifier Type: -

Identifier Source: org_study_id

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