Basal Like Bladder Cancer : Signature and Therapeutic

• Conditions: Molecular Taxonomy; Muscle Invasive Bladder Cancer
• Interventions: Other: biomarker study

• Registration Number: NCT02648100
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

Detailed Description

The aim of this study is:

1. 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.

2. 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)

3. 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 Timeline

• Study Start: 2014-03
• Study First Submitted: 2016-01-05
• Study First Submitted QC: 2016-01-05
• Study First Posted: 2016-01-06
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-19
• Last Update Posted: 2017-06-20
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 911

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
C	biomarker study	188 patients treated by cystectomy and adjuvant chemotherapy for locally advanced bladder cancer from a national multicentric study.
B	biomarker study	510 cystectomy patients operated between 2005 and 2010 in Henri Mondor and Foch hospitals.
A	biomarker study	120 patients from Carte d'Identité des Tumeurs (CIT), Henri Mondor and Foch hospitals.
D	biomarker study	93 patients from the clinical trial GETUG 19 (UNICANCER)

Primary Outcome Measures

Name	Time	Method
Progression free survival	5 years

Secondary Outcome Measures

Name	Time	Method
Overall survival	5 years
Specific survival	5 years

Trial Locations

Locations (1)

Henri Mondor Hospital; 🇫🇷 Creteil, France