Clinical trial NCT06181201: Association Between the Composition of the Intestinal Microbiota and Tumor Response in Locally Advanced Rectal Cancer
Official title: Association Between the Composition of the Intestinal Microbiota Before Treatment and the Tumor Response After Induction Chemotherapy Followed or Not by Neo-adjuvant Radio-chemotherapy in Locally Advanced Rectal Cancer
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Cancer of Rectum
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: L'Institut des sciences moléculaires (iSm2 UMR CNRS 7313)
First posted: 2023-12-26
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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

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;

Eligibility criteria: 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

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

Primary outcomes:
measure: Gut microbiota description at T0
timeFrame: at baseline
measure: histological response according to Ryan classification
timeFrame: after surgery, an average of 8 months after inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Mathias CHAMAILLARD
role: STUDY_DIRECTOR
affiliation: Centre Oscar Lambret
name: Mehrdad JAFARI
role: PRINCIPAL_INVESTIGATOR
References: