Phase I trial of RAD001 (R), bevacizumab (B), and docetaxel (D) for castration-resistant prostate cancer (CRPC)

5154 Background: Targeting of mTOR and vascular endothelial growth factor (VEGF) alone or with chemotherapy has been reported for CRPC. We report a dose finding study combining mTOR and VEGF inhibitors along with docetaxel for advanced CRPC. Methods: Eligible patients (pts) had progressive, metastatic, chemo-naive CRPC. A modified adaptive design was used to explore 3 dose levels. 3 pts were treated in each cohort, expanded by 3 pts if a dose limiting toxicity (DLT) was observed. If no DLT occurred after all pts completed 2 cycles in a cohort, pts were enrolled at the next dose level. If a DLT was seen in 2 pts, that dose level was closed. Dose levels included: cohort 1 (D 75 mg/m2, R 2.5 mg, B 15 mg/kg); cohort 2 (D 75 mg/m2, R 5 mg, B 15 mg/kg); and cohort 3 (D 65 mg/m2, R 5 mg, B 15 mg/kg). D+B was given IV day (d) 1 and R PO days 1–21 on a 21 d cycle. Efficacy is explored as: maximal confirmed PSA decline; partial or complete response (PR+CR) by RECIST criteria; and/or changes in bone scintigraphy. Re...