PROSENZA: Prospective multi-centre study of prognostic factors in castration resistant prostate cancer (CRPC) patients treated with enzalutamide (ENZ)

Abstract

Background: CRPC is a heterogeneous disease, and despite new agents approved, the optimal sequence of treatment remains unclear, far from personalised medicine that may offer the maximal benefit for the patient. For that reason, our aim is the identification of new biomarkers in CRPC patients treated with conventional therapy. Trial design: PROSENZA is a prospective multicentre observational study in metastatic CRPC designed to explore biomarkers in patients treated with ENZ. Key inclusion criteria: a) histological confirmation of prostate cancer; b) documented criteria (PCWG2) for CRPC; c) availability of tumour tissue; d) candidate for standard treatment with ENZ. Primary end point: to study the prognostic value for overall survival (OS) of the detection of androgen receptor splicing variant 7 (AR-V7) and/or amplification of AR (AR+) in peripheral blood in this cohort. Secondary end points: a) to analyse the correlation between PSA response and AR-V7 and/or AR+; b) to evaluate the correlation between radiological response and AR-V7 and/or AR+; c) to study changes in AR-V7 frequency and/or AR+ pre and post ENZ; d) to analyse and correlate the prognostic role of AR-V7 and AR+ with other biomarkers as testosterone serum levels, PTENloss or TMPRSS-ERG fusions. Exploratory outcomes: a) to validate in this cohort prognostic nomograms described for CRPC; b) to validate the prognostic role of the expression signature described by Olmos et al (Lancet Oncol 2012) in peripheral blood; c)to explore new somatic and germinal variants in peripheral blood and tissue associated to dissemination, response and resistance to ENZ. PROSENZA is part of the PROCURE Biomarkers network, a multicentric spanish platform for biomarkers discovery in CRPC. 187 patients will be accrued to provide appropriate statistical power to detect at least 71 events (deaths) to analyse the main outcome. Currently, 48 centres are active for recruitment and 54 patients have been included. Blood samples are collected before, during and after progression to ENZ Prospective data collection will be linked. This study may help to incorporate new biomarkers in clinical practice and improve the selection of therapy in mCRPC.