Evolution of Proteomic Profiles of Intestinal Microbiota in Patients With Locally Advanced or Metastatic Urothelial Carcinomas

NCT04566029 | Completed DMC

• 2 other identifiers: NIMAO2019_22020-A01224-35
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 10

Brief Summary

Immunotherapy has become an essential therapeutic weapon against many cancers. Control point inhibitors (CPI, PD-1/PD-L1) have shown efficacy in the therapeutic management of tumors in the bladder in progression after administering platinum derivatives. But only 20% of patients get any clinical benefit from these heavy treatments in the long term. Treating metastatic patients without distinction means taking a considerable risk of toxicity and generates major costs. It is therefore urgent and important to exceed the current criteria for using immunotherapy. Recent studies have shown the interest of studying intestinal microbiota as a marker of the efficacy of immunotherapy. The investigators hypothesized that the proteomic signature of the intestinal microbiota in patients with locally advanced or metastatic urothelial carcinomas who responded to immunotherapies was special, and has very different characteristics from that of patients with the same pathology who do not respond to immunotherapy.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Stool sample collected from patients in the "cases" group

  Quantification of bacterial proteins as a reflection of the intestinal microbiota and human proteins in the patient's stools. These will be analyzed from 50mg of stools via mass spectrometry (ESI-Q combined with the Ultimate 3000 Nano liquid chromatography system, ThermoFisher Scientific).

  24 hours before the patient's follow-up visit at 1 month +/- 7 days

• Stool sample collected from patients in the "controls" group

  Quantification of bacterial proteins as a reflection of the intestinal microbiota and human proteins in the patient's stools.These will be analyzed from 50mg of stools via mass spectrometry (ESI-Q combined with the Ultimate 3000 Nano liquid chromatography system, ThermoFisher Scientific).

  24 hours before the patient's follow-up visit at 1 month +/- 7 days

Secondary Outcomes (26)

• Immune system markers in patients with locally advanced or metastatic urothelial carcinomas in "cases" group patients.

  At the follow-up visit, 1 month +/- 7 days after inclusion

• Immune system markers in patients with locally advanced or metastatic urothelial carcinomas in "controls" group patients.

  At the follow-up visit, 1 month +/- 7 days after inclusion

• Evolution over time in the quality of life of patients in the "cases" group - EORTC QLQ-C30

  At the inclusion visit on Day 0

• Evolution over time in the quality of life of patients in the "cases" group - EORTC QLQ-C30

  At the follow-up visit, 1 month +/- 7 days after inclusion

• Evolution over time in the quality of life of patients in the "cases" group - EORTC QLQ-C30

  At the end of study visit, 2 months +/- 15 days after inclusion

Study Arms (2)

Cases

Patients who have been responding to treatment for a long time

Biological: Blood test; Biological: Stool sample; Other: Questionnaires

Controls

Patients who do not respond to treatment

Biological: Blood test; Biological: Stool sample; Other: Questionnaires

Interventions

Blood test BIOLOGICAL

The patients' blood will be collected in four 5mL heparinized tubes

Cases; Controls

Stool sample BIOLOGICAL

The patients' stools will be collected at home

Cases; Controls

Questionnaires OTHER

At each visit, the following questionnaires will be collected: QLQ-C30 and EQ5D-5L Appendix 16.2 and PRO CTCAE

Cases; Controls

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients who are affiliated to or covered by a health insurance scheme. All patients over the age of 18.

You may qualify if:

• For the "controls" group:
• Patients undergoing treatment for a locally advanced or metastatic urothelial tumor
• Patients who have been on immunotherapy and 2nd-line monotherapy treatment for at least 6 months for a non-operable disease
• Patients whose immunotherapy has been interrupted due to progression of the disease
• For the "cases" group:
• patients being treated in the context of a temporary authorization for use delivered for atezolizumab for the management of locally advanced or metastatic urothelial carcinomas following treatment based on platinum salts and still on treatment or patients being treated with pembrolizumab in the context of a donation for compassionate reasons (and still on treatment).

You may not qualify if:

• Patients who do not speak or read the French language.
• Patients under legal guardianship or curatorship.
• Patients for whom it is impossible to give clear information to.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead
• European Georges Pompidou Hospital: collaborator
• ICM Montpellier: collaborator
• IUCT Oncopole (Toulouse): collaborator
• Institut de cancérologie Strasbourg Europe: collaborator
• Institut de Cancérologie Lucien Neuwirth (Saint Etienne): collaborator
• ICO - SITE Paul Papin: collaborator
• Centre Antoine Lacassagne: collaborator
• Institut Bergonié: collaborator
• Tenon Hospital, Paris: collaborator

Study Sites (10)

ICM parc euromedecine

Montpellier, Hérault, 34298, France

Location

Hopital Tenon ( Paris)

Paris, Paris Cx 20, 75970, France

Location

Institut Sainte Cancerologie Lucien Neuwirth

Avignon, Saint Priest En Jarez, 42271, France

Location

ICO-Site Paul Papin

Angers, 49055, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

HEGP GH Universitaire Paris Ouest

Paris, 75908, France

Location

ICANS Strasbourg

Strasbourg, 67091, France

Location

Iuct Oncopole

Toulouse, 31059, France

Location

Related Publications (2)

• Annakib S, Fiteni F, Houede N. Quality of Life with Monoclonal Antibody Therapies for Locally Advanced or Metastatic Urothelial Carcinoma: A Systematic Review. Eur Urol Oncol. 2023 Oct;6(5):467-476. doi: 10.1016/j.euo.2023.05.001. Epub 2023 May 25.

  PMID: 37244802 RESULT

• Annakib S, Di Meglio E, Dibert-Bekoy Y, Chevallier T, Roubaud G, Fournel P, Guillot A, Borchiellini D, Pouessel D, Boughalem E, Delva R, Barthelemy P, Oudard S, Thibault C, Tosi D, Houede N, Fiteni F. Patient Versus Clinician Reported Symptoms Agreement in Advanced Metastatic Bladder Cancer Patients. Cancer Med. 2025 Apr;14(8):e70896. doi: 10.1002/cam4.70896.

  PMID: 40256972 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and stool samples

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Hematologic Tests; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: September 28, 2020
• Study Start: December 12, 2020
• Primary Completion: November 29, 2022
• Study Completion: November 29, 2022
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

FR (10)