A Phase III of Cabazitaxel and Pelvic Radiotherapy in Localized Prostate Cancer and High-risk Features of Relapse

Eligible patients can be randomized via the TENALEA web site process that insure centralization of the randomization. Randomization will be performed according a 1:1:1:1 ratio. The randomization will be stratified (by minimization) according to the number of risk factors (2 vs.3), disease extent (pN- vs. pN+ vs. pNx) and the site. The minimization will be defined with a similar weight for all 3 stratification factors and a probability of assigning the treatment that minimize the imbalance equal to 80%. The main analysis of progression-free survival (PFS) will be event driven (\> 247 events). It will likely be performed when the median follow-up is approximately 6 years, i.e. 4 years after the inclusion of the last patient (assuming an accrual of 4 years). A long-term analysis (allowing for robust PFS and overall survival (OS) data) will also be performed when the follow-up is approximately 10 years. Its exact timing will be discussed with the steering committee and the IDMC. An interim analysis of the primary endpoint is planned. This interim analysis will be performed at a 0.001 level (Peto) after 50% of the events i.e. 125 have occurred. For each comparison (CT comparison and pelvic RT comparison) the two PFS curves will be compared using the adjusted logrank test (bilateral test): adjusted logrank on pelvic RT for the CT comparison and on CT for the pelvic RT comparison. A multivariate analysis using the Cox model will also be used. An Independent Data Monitoring Committee (IDMC) composed of international experts (at least 2 physicians and 1 statistician) will be selected. For safety purpose, the IDMC will meet after the inclusion of 20 patients (and then again after accrual of 50 patients) in the cabazitaxel and pelvic radiotherapy arm, to assess tolerance, (i.e. after the inclusion of approximately 80 and then 200 patients in the trial). Depending on the results of this feasibility phase and of any new relevant clinical results in such a population, the remaining patients (n=848) will be enrolled. During this second phase, the IDMC will then meet every two years approximately during accrual to carefully assess accrual rate and toxicity and examine the efficacy interim analysis results in the light of the results of similar trials.