Evolution of Proteomic Profiles of Intestinal Microbiota in Patients With Locally Advanced or Metastatic Urothelial Carcinomas
- Conditions
- Urothelial Carcinoma
- Interventions
- Biological: Blood testBiological: Stool sampleOther: Questionnaires
- Registration Number
- NCT04566029
- Lead Sponsor
- Centre Hospitalier Universitaire de NÄ«mes
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
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).
- Patients who do not speak or read the French language.
- Patients in an exclusion period determined by another study.
- Patients under legal guardianship or curatorship.
- Patients for whom it is impossible to give clear information to.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cases Blood test Patients who have been responding to treatment for a long time Cases Stool sample Patients who have been responding to treatment for a long time Controls Stool sample Patients who do not respond to treatment Cases Questionnaires Patients who have been responding to treatment for a long time Controls Blood test Patients who do not respond to treatment Controls Questionnaires Patients who do not respond to treatment
- Primary Outcome Measures
Name Time Method Stool sample collected from patients in the "cases" group 24 hours before the patient's follow-up visit at 1 month +/- 7 days 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).
Stool sample collected from patients in the "controls" group 24 hours before the patient's follow-up visit at 1 month +/- 7 days 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).
- Secondary Outcome Measures
Name Time Method Evolution over time in the quality of life of patients in the "cases" group - EQ5D-5L At the end of study visit, 2 months +/- 15 days after inclusion The EQ-5D (EuroQoL -5 Dimension) self-report questionnaire will be used to measure the quality of life under various health conditions and treatments according to 5 dimensions: mobility, personal autonomy, everyday living activities, pain/discomfort and anxiety/depression. There are 3 versions of this questionnaire: EQ-5D-3L with 3 levels of severity for each dimension, EQ-5D-5L with 5 levels of severity for each dimension and EQ-5D-Y which is the children's version. Each version is available in several languages. The questionnaire has 2 pages : page one with 5 items representing the 5 dimensions and page two with a visual analogue scale graded from 0 to 100 with 100 as the best possible state of health. For each dimension the patient must indicate what condition he/she is in. When all the answers are combined, a 5-figure number is obtained, indicating the patient's health condition. For example, the number 11111 shows that there are no problems in any of the 5 dimensions.
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 For each patient in the "cases" group, blood will be collected in four heparinized tubes and the immune populations will be studied via mass spectrometry (CyTOF/Helios). The frequency of the subpopulations thus determined will be compared between the two groups of patients (responders vs non responders) in order to identify those populations which are significantly different.
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 For each patient in the "controls" group, blood will be collected in four heparinized tubes and the immune populations will be studied via mass spectrometry (CyTOF/Helios). The frequency of the subpopulations thus determined will be compared between the two groups of patients (responders vs non responders) in order to identify those populations which are significantly different.
Evolution over time in the quality of life of patients in the "controls" group - EQ5D-5L At the end of study visit, 2 months +/- 15 days after inclusion The EQ-5D (EuroQoL -5 Dimension) self-report questionnaire will be used to measure the quality of life under various health conditions and treatments according to 5 dimensions: mobility, personal autonomy, everyday living activities, pain/discomfort and anxiety/depression. There are 3 versions of this questionnaire: EQ-5D-3L with 3 levels of severity for each dimension, EQ-5D-5L with 5 levels of severity for each dimension and EQ-5D-Y which is the children's version. Each version is available in several languages. The questionnaire has 2 pages : page one with 5 items representing the 5 dimensions and page two with a visual analogue scale graded from 0 to 100 with 100 as the best possible state of health. For each dimension the patient must indicate what condition he/she is in. When all the answers are combined, a 5-figure number is obtained, indicating the patient's health condition. For example, the number 11111 shows that there are no problems in any of the 5 dimensions.
Side-effects related to immunotherapy in "controls" group - patient's viewpoint. At the end of study visit, 2 months +/- 15 days after inclusion The NCI PRO-CTCAE (National Cancer Institute - Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) scale will be used to evaluate the side-effects of treatment so that they can be declared for clinical studies in cancerology. The measurement of the result is declared directly by the patient based on the last seven days of treatment. The choice of terms and the categories of toxicity depend on the adverse events targeted. A French version is available on the following link: https://healthcaredelivery.cancer.gov/pro-ctcae/countries.html. The questionnaire for this particular study will be created on the PROCTCAE website via the option "build a custom form" (https://healthcaredelivery.cancer.gov/pro-ctcae/builder.html). 20 symptoms or side effects that may occur during treatment will be selected to build a patient-reported outcomes questionnaire adapted to the study.
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 The quality of life will be evaluated via the EORTC QLQ-C30 questionnaire. The quality of life questionnaire designed by the European Organisation for Research and Treatment of Cancer known as EORTC QLQ-C30 is for all cancer patients, whatever the location of their cancer. It consists of 30 items grouped together into 15 dimensions. There are 4 possible answers to the first 28 items and 7 possible answers to the last 2 questions. The answers take the form of a Lickert scale.
Evolution over time in the quality of life of patients in the "controls" group - EORTC QLQ-C30 At the end of study visit, 2 months +/- 15 days after inclusion The quality of life will be evaluated via the EORTC QLQ-C30 questionnaire. The quality of life questionnaire designed by the European Organisation for Research and Treatment of Cancer known as EORTC QLQ-C30 is for all cancer patients, whatever the location of their cancer. It consists of 30 items grouped together into 15 dimensions. There are 4 possible answers to the first 28 items and 7 possible answers to the last 2 questions. The answers take the form of a Lickert scale.
Side-effects related to immunotherapy in "cases" group - patient's viewpoint. At the end of study visit, 2 months +/- 15 days after inclusion The NCI PRO-CTCAE (National Cancer Institute - Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) scale will be used to evaluate the side-effects of treatment so that they can be declared for clinical studies in cancerology. The measurement of the result is declared directly by the patient based on the last seven days of treatment. The choice of terms and the categories of toxicity depend on the adverse events targeted. A French version is available on the following link: https://healthcaredelivery.cancer.gov/pro-ctcae/countries.html. The questionnaire for this particular study will be created on the PROCTCAE website via the option "build a custom form" (https://healthcaredelivery.cancer.gov/pro-ctcae/builder.html). 20 symptoms or side effects that may occur during treatment will be selected to build a patient-reported outcomes questionnaire adapted to the study.
Side-effects related to immunotherapy in "cases" group - clinician's viewpoint. At the end of study visit, 2 months +/- 15 days after inclusion Version 4.03 of the NCI-CTCAE (National Cancer Institute- Common Terminology Criteria for Adverse Events) scale in French will be used to declare adverse events. It has 26 categories describing over 300 undesirable events, graded according to their severity (5 grades, each with its unique medical term). Grade 1 = Slight; asymptomatic or slight symptoms, only diagnosed upon clinical examination, requiring no treatment. Grade 2 = Moderate; requiring minimum local or non-invasive treatment; interfering with instrumental activities of daily living.Grade 3 = Severe or medically significant but vital prognosis is not compromised. Indication for hospitalisation or prolongation of hospitalisation, invalidating, interfering with simple activities of daily living. Grade 4 = vital prognosis compromised, requiring emergency management. Grade 5 = Death due to the adverse event. Not all grades are appropriate for all adverse events and therefore some are listed with a choice of below Grade 5.
Side-effects related to immunotherapy in "controls" group - clinician's viewpoint. At the end of study visit, 2 months +/- 15 days after inclusion Version 4.03 of the NCI-CTCAE (National Cancer Institute- Common Terminology Criteria for Adverse Events) scale in French will be used to declare adverse events. It has 26 categories describing over 300 undesirable events, graded according to their severity (5 grades, each with its unique medical term). Grade 1 = Slight; asymptomatic or slight symptoms, only diagnosed upon clinical examination, requiring no treatment. Grade 2 = Moderate; requiring minimum local or non-invasive treatment; interfering with instrumental activities of daily living.Grade 3 = Severe or medically significant but vital prognosis is not compromised. Indication for hospitalisation or prolongation of hospitalisation, invalidating, interfering with simple activities of daily living. Grade 4 = vital prognosis compromised, requiring emergency management. Grade 5 = Death due to the adverse event. Not all grades are appropriate for all adverse events and therefore some are listed with a choice of below Grade 5.
Trial Locations
- Locations (10)
Hopital Tenon ( Paris)
🇫🇷Paris, Paris Cx 20, France
Centre Antoine Lacassagne
🇫🇷Nice, France
ICM parc euromedecine
🇫🇷Montpellier, Hérault, France
Institut Bergonié
🇫🇷Bordeaux, France
Institut Sainte Cancerologie Lucien Neuwirth
🇫🇷Avignon, Saint Priest En Jarez, France
ICO-Site Paul Papin
🇫🇷Angers, France
Centre Leon Berard
🇫🇷Lyon, France
ICANS Strasbourg
🇫🇷Strasbourg, France
Iuct Oncopole
🇫🇷Toulouse, France
HEGP GH Universitaire Paris Ouest
🇫🇷Paris, France