Phase II Study of RAD001 in a Neoadjuvant Setting in Men With Intermediate or High Risk Prostate Cancer

Newly diagnosed patients with prostate cancer, with localized untreated disease must be at intermediate or high risk for disease relapse based on their PSA, Gleason score, and clinical stage. Before starting treatment, a baseline radiographic evaluation with FDG-PET and magnetic resonance imaging (MRI) will be performed. Biopsies will also be performed to obtain fresh tissue for molecular and gene expression assays. In patients with a positive FDG-PET scan at baseline, Treatment Day 1-14 will be with RAD001 10 mg/day alone. After performing post-RAD001 FDG-PET evaluation, treatment Day 15 will be equivalent of Treatment Day 1 of the trial in patients with negative FDG-PET scan at baseline. In patients with a negative FDG-PET scan at baseline, Treatment Day 1 is the beginning of the Phase II trial of RAD001 combined with androgen ablation treatment. Patients will be treated with RAD001 10 mg per day combined with androgen ablation therapy for 8 weeks depending on their ability to tolerate the drug. Radiographic and biologic assays will be repeated after 8 weeks, at which time patients will undergo prostatectomy or external beam radiation therapy (ERT). Second biopsy will be performed in patients admitted to ERT They will receive RAD001 up to the day of surgery or ERT to ascertain better tissue concentration of the drug. Gene expression profiling will also be evaluated at that time. The primary endpoint of this study is pharmacodynamic assessments of the effects of RAD001 in prostate cancer. However, the secondary endpoints of this study will define its true success. Specifically, the study will evaluate pharmacodynamic assessments of the effects of RAD001 in prostate cancer using novel applications of radiology, molecular biology, and genomics. These novel endpoints will be correlated with more established pathologic measures, such as microvessel density, apoptotic indexes, PTEN, phospho-AKT and phospho-p70S6K. MRI and 3-dimensional. PSA effects will also be assessed. Prostate cancer tissues from high risk prostate cancer patients admitted to neoadjuvant androgen ablation without RAD001 will serve as controls. An ambitious aspect of this project is to examine gene expression alterations that occur in these patients. It will be technically challenging to get enough tissue by needle biopsies for gene array analysis. However, clearly, obtaining this information might be very useful in describing the full effects of RAD001 therapy in this patient population.