Basal Like Bladder Cancer : Signature and Therapeutic

NCT ID: NCT02648100

Last Updated: 2017-06-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

911 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-03-31

Study Completion Date

2019-12-31

Brief Summary

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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

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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.

Conditions

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Muscle Invasive Bladder Cancer Molecular Taxonomy

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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A

120 patients from Carte d'Identité des Tumeurs (CIT), Henri Mondor and Foch hospitals.

biomarker study

Intervention Type OTHER

B

510 cystectomy patients operated between 2005 and 2010 in Henri Mondor and Foch hospitals.

biomarker study

Intervention Type OTHER

C

188 patients treated by cystectomy and adjuvant chemotherapy for locally advanced bladder cancer from a national multicentric study.

biomarker study

Intervention Type OTHER

D

93 patients from the clinical trial GETUG 19 (UNICANCER)

biomarker study

Intervention Type OTHER

Interventions

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biomarker study

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

National Cancer Institute, France

OTHER_GOV

Sponsor Role collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

Paris 12 Val de Marne University

OTHER

Sponsor Role collaborator

Institut Curie

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yves ALLORY, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Henri Mondor Hospital

Créteil, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Yves ALLORY, MD, PhD

Role: CONTACT

(0)1 49 81 27 29 ext. +33

François RADVANYI, PhD

Role: CONTACT

(0)1 42 34 63 39 ext. +33

Other Identifiers

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NI 13021

Identifier Type: -

Identifier Source: org_study_id

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