A randomized phase II study of pazopanib in hormone sensitive prostate cancer: a University of Chicago Phase II Consortium/ Department of Defense Prostate Cancer Clinical Trials Consortium study

BACKGROUND: Intermittent androgen suppression (1) is an increasingly popular treatment option for hormone sensitive prostate cancer. Based on previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor (VEGFR) using pazopanib during the IAS off period would result in prolonged time to PSA failure. METHODS: Men with biochemically recurrent prostate cancer whose PSA was < 0.5 ng/mL after 6 months of androgen deprivation therapy (ADT) were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng/mL. RESULTS: Thirty-seven patients were randomized. Of 18 randomized to pazopanib, at the time of study closure, 4 had progressive disease (PD), 1 remained on treatment, and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had PD, 7 remained under protocol defined observation, and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Due to high dropout rates in both arms, the study was halted. CONCLUSIONS: IAS is a treatment approach that may facilitate investigation of novel agents in the hormone sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience in order to reduce the drop out rate.