Phase II trial of RAD001 and bicalutamide for castration-resistant prostate cancer

OBJECTIVES To determine best overall response and duration of response of RAD001, a selective inhibitor of mammalian target of rapamycin, in combination with bicalutamide in castration-resistant prostate cancer (CRPC). To characterize the toxicity profile of RAD001 in combination with bicalutamide in patients with CRPC. PATIENTS AND METHODS A phase II study was conducted to explore the efficacy and tolerability of RAD001 (10 mg daily) in combination with bicalutamide (50 mg daily) in men with progressive CRPC. The primary endpoint was a composite of prostate-specific antigen (PSA) level and measurable disease response by standard criteria. This single-stage trial with a sample size of 38 eligible patients provided 90% power to differentiate a response rate of =40% from a response rate of =20%, as expected for bicalutamide alone (a= 0.10, power = 0.90). RESULTS In total, 36 men were enrolled, with a median (range) age of 68 (6072) years and median (range) baseline PSA level of 22.2 (8.4121.3) ng/mL, and 89% had metastatic disease. There were 31 (86%) patients had previously used bicalutamide for a median duration of 7.4 months. There were two patients with a confirmed PSA level decline =50%. The median (interquartile range) time to progression was 8.7 (7.915.9) weeks. The most common toxicity was grade 1/2 mucositis, which was observed in 20 (56%) patients. CONCLUSION The combination of RAD001 and bicalutamide in men with CRPC was well tolerated but had low activity and failed to achieve the primary endpoint of improved response compared to the results previously achieved for bicalutamide alone in this population.