Clinical trial NCT02648100: Basal Like Bladder Cancer : Signature and Therapeutic
Official title: Identification and Treatments of Basal Like Bladder Cancer (Study on Human Tumor Samples and Animal Models)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Muscle Invasive Bladder Cancer
Molecular Taxonomy
Keywords: Muscle invasive bladder cancer
Basal subtype
Anti-EGFR treatment
Nanostring
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: National Cancer Institute, France
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Paris 12 Val de Marne University
name: Institut Curie
First posted: 2016-01-06
Enrollment: 911
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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)

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Specific survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Creteil
country: France
facility: Henri Mondor Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Yves ALLORY, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: