Phase II Study of RAD001 in a Neoadjuvant Setting in Men With Intermediate or High Risk Prostate Cancer
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
The mechanisms responsible for the development of hormonal refractory prostate cancer (HRPC)
have been elusive. Genetic inactivation/loss of the PTEN tumor suppressor gene occurs in
30-60% of advanced prostate cancers and in 20% of the localized form. Researchers hypothesize
that PTEN loss is a landmark genetic event in prostate cancer progression into the fatal HRPC
form. One consequence of PTEN loss is activation of the oncogenic Akt and phosphorylation of
downstream Akt targets including mTOR. mTOR controls many important cellular processes
including cell cycle regulation.
We propose to evaluate pharmacodynamic assessments of the mTOR inhibitor RAD001 in
intermediate and high risk prostate cancer patients in the neoadjuvant setting. Patients will
be admitted to 6 weeks treatment with RAD001 10 mg/day followed by either radical
prostatectomy or radiotherapy combined with hormonal treatment. Immunohistochemistry with
antibodies for phosphorylated p70S6K , pS6, Akt as well as antibodies for VEGF, BCL2 and PTEN
in prostate cancer tissues before and after 6 weeks RAD001 treatment will be performed.
Additionally, Patients will be evaluated by FDG-PET scan before (as baseline) and after
RAD001 treatment. A link between mTOR signaling and glycolysis regulation was established and
may provide a mechanism to assess drug-target interaction of RAD001 in prostate cancer.
The secondary endpoint of the trial will be to determine the response proportion to RAD001
treatment by assessing time to biochemical failure followed by radiation therapy or radical
prostatectomy. The data will be compared to a matched cohort of high and intermediate-risk
prostate cancer patients admitted to the same treatments modalities without receiving RAD001.