Basal Like Bladder Cancer : Signature and Therapeutic (DIATRIBBE)
June 19, 2017 updated by: Assistance Publique - Hôpitaux de Paris
Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)
Muscle invasive (MIBC) and/or metastatic bladder cancer is associated with poor prognosis and no target therapies for this pathology are currently validated.
By 40 gene expression signature realized on frozen samples, we have previously identified an aggressive sub-class of MIBC, called basal.
This sub-class (20% of MIBC) showed strong EGFR dependence in vitro and in vivo (Rebouissou et al.
Science Translational Medicine 2014).
This observation suggests a possible response to EGFR targeted therapy in patients of this subgroup.
Our aim is to establish a standard diagnostic tool to differentiate the basal subtype of bladder cancer and evaluate the effect of anti-EGFR therapy, by analyzing previous clinical trial (GETUG19) and preclinical models, which compare the classical chemotherapy to anti-EGFR associated chemotherapy.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
Detailed Description
The aim of this study is:
- To validate a diagnostic test for formalin-fixed paraffin-embedded (FFPE) samples by Nanostring technology, using the 40 genes signature as reference. First, we will compare frozen and FFPE tissues (n=120), to establish a transcriptional signature in FFPE samples. Secondly, to further characterize basal subtype of bladder cancer, we will study the mutational and gain/loss landscape and immunohistochemistry markers in a new series of tumors after classifying them by our gene signature (n=510). These characteristics will be included in a new signature by defining the optimal prediction discrimination AIC et Net Reclassification Index.
- To assess the prognosis after cisplatine treatment in 510 patients treated by cystectomy with or without adjuvant chemotherapy (pT2/pT3/pT4, N0 or N+) and in another multicentric series of 188 patients treated by cystectomy and adjuvant chemotherapy (pT3/pT4 et/ou N+). Uni and multi variant analysis will be realized by adjusted Cox model, and the added value of basal subtype as compared to standard prognostic factors will be evaluated. The propensity score will be realized to assess the association of basal subtype and response to chemotherapy. The anti-EGFR response will be analyzed in the clinical trial GETUG19 which uses Panitumumab in patients with metastatic urothelial carcinomas (n=93)
- To study the treatment response in preclinical models. We characterized previously preclinical murine models derived from xenografts of MIBC (n=14 and new xenografts will be added). We will study the effect of anti-EGFR alone or in combination with chemotherapy in basal and non basal subtypes of xenografts.
By this study we will be able to better characterize the basal subtype of bladder cancer and confirm its aggressive behaviour as compared to other subtypes of MIBC. These results will further help to establish new clinical trials which include anti-EGFR in patients of basal subtype.
Study Type
Observational
Enrollment (Anticipated)
911
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Creteil, France, 94010
- Recruiting
- Henri Mondor Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Patients with Bladder Cancer from 4 cohorts
- 2 observational cohorts of patients with muscle invasive bladder cancer (all stages) from two Henri Mondor (Créteil) and Foch (Suresnes) hospitals
- 1 multicentric observational cohort of patients with locally advanced muscle invasive bladder cancer trated by adjuvantchemotherapy after cystectomy
- 1 clinical trial GETUG 19 (MVAC + panitumumab)
Description
Inclusion Criteria:
Muscle invasive bladder cancer Treatment by cystectomy Adjuvant chemotherapy for 3rd cohort Clinical trial GETUG 19 for 4th cohort
Exclusion Criteria:
FFPE material not available Follow-up data not available
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
A
120 patients from Carte d'Identité des Tumeurs (CIT), Henri Mondor and Foch hospitals.
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B
510 cystectomy patients operated between 2005 and 2010 in Henri Mondor and Foch hospitals.
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C
188 patients treated by cystectomy and adjuvant chemotherapy for locally advanced bladder cancer from a national multicentric study.
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D
93 patients from the clinical trial GETUG 19 (UNICANCER)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Progression free survival
Time Frame: 5 years
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Overall survival
Time Frame: 5 years
|
5 years
|
|
Specific survival
Time Frame: 5 years
|
5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Yves ALLORY, MD, PhD, Assistance Publique - Hôpitaux de Paris
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2014
Primary Completion (Anticipated)
December 1, 2019
Study Completion (Anticipated)
December 1, 2019
Study Registration Dates
First Submitted
January 5, 2016
First Submitted That Met QC Criteria
January 5, 2016
First Posted (Estimate)
January 6, 2016
Study Record Updates
Last Update Posted (Actual)
June 20, 2017
Last Update Submitted That Met QC Criteria
June 19, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NI 13021
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
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