Basal Like Bladder Cancer : Signature and Therapeutic (DIATRIBBE)

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: Muscle Invasive Bladder Cancer; Molecular Taxonomy
• Intervention / Treatment: Other: biomarker study

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 Type: Observational
• Enrollment (Anticipated): 911

Contacts and Locations

• Study Contact: Name: Yves ALLORY, MD, PhD; Phone Number: +33 (0)1 49 81 27 29; Email: yves.allory@aphp.fr
• Study Contact Backup: Name: François RADVANYI, PhD; Phone Number: +33 (0)1 42 34 63 39; Email: francois.radvanyi@curie.fr

Study Locations

• France
  • Creteil, France, 94010
    • Recruiting
    • Henri Mondor Hospital

Participation Criteria

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

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	5 years
Specific survival	5 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Ministry of Health, France; National Cancer Institute, France; Institut Curie; Paris 12 Val de Marne University
• Investigators: Principal Investigator: Yves ALLORY, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

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

• Keywords: Basal subtype; Muscle invasive bladder cancer; Nanostring; Anti-EGFR treatment
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: NI 13021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes