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.
Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Israel: Israeli Health Ministry Pharmaceutical Administration