Association Between the Composition of the Intestinal Microbiota and Tumor Response in Locally Advanced Rectal Cancer

Terminated

• Conditions: Cancer of Rectum
• Interventions: Procedure: Stool collection

• Registration Number: NCT06181201
• Lead Sponsor: Centre Oscar Lambret

Brief Summary

This is an observational, single-centre study (RIPH3) for patients with rectal cancer soon to be treated with chemotherapy (+/- neo-adjuvant radio-chemotherapy) looking at the relationship between the composition of the gut microbiota before treatment and the tumour response after chemotherapy +/- radio-chemotherapy

Detailed Description

Main objective: The main objective is to test the association between :

* the gut microbiota assessed from a stool sample before the start of neoadjuvant treatment of patients (T0) on the one hand, and

* complete histological response assessed on the surgical resection specimen in patients with histologically proven stage II and III rectal tumours treated with neo-adjuvant chemotherapy followed or not by Cap50 radiochemotherapy before surgery.

Primary endpoint: The primary endpoint will be complete histological response assessed on the surgical specimen after the neoadjuvant therapy regimen. This assessment will be performed according to the usual standards and blinded to any information on the gut microbiota and on the content of short-chain fatty acids and tryptophan derivatives.

Secondary objectives:

* To explore the profile of gut microbiota composition and short-chain fatty acid content in the two groups of patients (complete histological response or not), assessed before any treatment (T0).

* To assess the changes in the composition of the intestinal flora and the content of short chain fatty acids following treatment with induction chemotherapy (T1), then preoperative radiochemotherapy (T2) if applicable, by comparison of the preoperative sample with the initial sample (T0).

* Assess the association between these taxonomic and metabolic changes (T1-T0, T2-T0) on the one hand and the histological response on the other.

* To evaluate the association between the profile of the composition of the intestinal microbiota and the content of short-chain fatty acids, as well as calprotectin (a reliable and sensitive non-invasive marker of intestinal inflammation) assessed before any treatment (T0) on the one hand, and the occurrence of toxicity during treatment, in particular digestive toxicity.

Secondary endpoints:

* Percentage of different bacteria or families of bacteria (abundance) such as Ruminococcaceae in the intestinal flora and dosage of short-chain fatty acids;

* Rarefaction curves;

* Taxonomic indicators;

* Alpha and beta diversity indices of microbiota composition;

* Determination of calprotectin by ELISA on stool sample.

* Toxicity assessed by collecting adverse events during treatment with FOLFIRINOX and for some patients during radiochemotherapy, graded according to the NCI CTCAE v5 scale and classified according to the MEDDRA dictionary;

Study Timeline

• Study First Submitted: 2022-12-06
• Study First Submitted QC: 2023-12-12
• Study First Posted: 2023-12-26
• Study Start: 2024-01-19
• Primary Completion: 2024-10-08
• Study Completion: 2024-10-08
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Histologically proven stage II and III adenocarcinoma of the lower and middle rectum
• Patient undergoing preoperative treatment with induction chemotherapy (Folfirinox) followed or not by radio-chemotherapy of the Cap50 type
• Male or female patient aged 18 years or older
• Normal weight, overweight or moderately obese (BMI between 18.5 and 34.9)
• Patient residing in the Lille metropolitan area
• Patient affiliated to a French social protection scheme
• Patient having given his non-opposition

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Exclusion Criteria

• History of other concurrent cancers
• Presence of an intestinal (internal or external) or external urinary diversion
• Uncooperative patient for geographical, family, social or psychological reasons
• Limited legal capacity or legal incapacity

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Person with rectal cancer	Stool collection	People with locally advanced rectal cancer who are to receive induction chemotherapy with FLOFIRINOX followed or not by neo-adjuvant radio-chemotherapy of the Cap50 type.

Primary Outcome Measures

Name	Time	Method
Gut microbiota description at T0	at baseline	gut microbiota assessed from a stool sample before the start of neoadjuvant treatment of patients (T0) Measurement of gut microbiota composition at T0 by high-throughput sequencing of the 16S subunit of bacterial ribosomes
histological response according to Ryan classification	after surgery, an average of 8 months after inclusion	complete histological response assessed on the surgical resection specimen in patients with histologically proven stage II and III rectal tumours treated with neo-adjuvant chemotherapy followed or not by Cap50 radiochemotherapy before surgery and according to Ryan classification.; TRG (TRG0-TRG3) TRG 3: extensive residual cancer with no evident tumor regression (poor or not response

Trial Locations

Locations (1)

Centre Oscar Lambret; 🇫🇷 Lille, France