SECOND RANDOMIZED TRIAL TO COME
CARD: A randomized phase 4 trial comparing cabazitaxel and an androgen receptor (AR)-targeted agent in men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and an alternative AR-targeted agent
Background: mCRPC is highly heterogeneous with coexistence of AR-dependent and AR-independent tumor clones. New AR-targeted agents (abiraterone acetate, enzalutamide) and taxanes (docetaxel (DOC), cabazitaxel - specifically developed to overcome DOC resistance) are the backbone of mCRPC therapy. The rising concern of cross-resistance between mCRPC therapies and the evidence that some patients may not respond to all available drugs have increased the complexity of managing mCRPC. There is thus a need to design trials helping to define the optimal sequence of therapies to optimize patient outcomes.
Trial design: CARD is a randomized phase 4 trial involving 79 sites in 12 European countries. A total of 324 patients with mCRPC previously treated with DOC and who failed a prior AR-targeted agent (abiraterone acetate or enzalutamide, either before or after DOC) within 12 months of AR-targeted treatment initiation will be randomized (1:1) to receive cabazitaxel (25mg/m2 every 3 weeks plus daily prednisone and prophylactic G-CSF) or the alternative AR-targeted agent until radiographic progression, unacceptable toxicity or patient's request. Randomization will be stratified by ECOG performance status (0-1 vs. 2), time to progression with prior AR-targeted agent (<6 vs. 6-12 months) and timing of AR-targeted agent (before or after DOC). The primary endpoint is radiological progression-free survival (rPFS) as per PCWG2 definition (Scher, JCO 2008; 26:1148-1159). Secondary endpoints include overall survival, objective tumor response and its duration, PSA response, time to PSA progression/ radiographic progression/ pain progression/ first symptomatic skeletal event, quality of life (FACT-P), health status/utility (EQ5D-5L), safety and the Epic Sciences CTC signature of resistance to AR-targeted agents. rPFS will be analyzed using 2-sided log-rank test adjusted for stratification factors. The trial has 90% power to detect a hazard ratio of 0.67, at a significance level of 0.05. Kaplan-Meier estimates/curves will be produced for both treatment groups. The CARD trial is currently recruiting.
Clinical trial identification: NCT02485691