A randomized phase II study comparing cabazitaxel/prednisone to cabazitaxel alone in docetaxel-pretreated men with metastatic castration resistant prostate cancer (mCRPC): The CABACARE trial

TPS345 Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients (Pts). Whether daily PDN may significantly contribute to CAB efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are scarce. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect CAB clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE (EudraCT 2016-005251-25) is a randomized, phase II, open label, multi-center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective (non-inferiority HR = 1.4). Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events . The influence of AR-V7 and RB status measured in circulating epithelial cells at baseline on CAB activity will also be evaluated. A total of 35 Italian centers have started / will start recruiting pts in the CABACARE trial. Of the 220 pts required by the trial design, 43 pts have been enrolled since 30th Nov , 2017 until 2nd Oct, 2018 in 10 different Italian Institutions. Clinical trial information: 2016-005251-25.