Basal Like Bladder Cancer : Signature and Therapeutic

Muscle Invasive Bladder Cancer Clinical Trial

— DIATRIBBE  

Official title:

Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02648100
• Other study ID #: NI 13021
• Status: Recruiting
• Phase: N/A
• First received: January 5, 2016
• Last updated: June 19, 2017
• Start date: March 2014
• Est. completion date: December 2019

Study information

• Verified date: June 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Yves ALLORY, MD, PhD
• Phone: (0)1 49 81 27 29
• Email: yves.allory[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 911
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Molecular Taxonomy
• Muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Other:
• biomarker study

Locations

Country	Name	City	State
France	Henri Mondor Hospital	Creteil

Sponsors (6)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	INSERM (French National Medicine Research Agency), Institut Curie, Ministry of Health, France, National Cancer Institute, France, Paris 12 Val de Marne University

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival		5 years
Secondary	Overall survival		5 years
Secondary	Specific survival		5 years