Randomized Phase II Study of Two Different Doses of RAD-001 (Everolimus) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed newly diagnosed, localized adenocarcinoma
of the prostate, meeting any of the following criteria:

- Clinical stage T2a, T2b, T2c, or T3 disease (any grade or PSA)

- Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA)

- Serum PSA ≥ 10 ng/dL (any grade or stage)

- Any stage, PSA, or Gleason score AND ≥ 35% chance of biochemical failure at 5
years based on Kattan's nomogram

- Recommended for radical prostatectomy

- Normal testosterone level

- No pure neuroendocrine or small cell prostate cancer

- No metastatic disease by CT scan, MRI, bone scan, or X-ray

- No clinical evidence of CNS metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%

- ANC ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Hemoglobin ≥ 8 g/dL

- AST and ALT ≤ 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- Creatinine ≤ 1.5 times ULN

- PT/PTT normal (no anticoagulants)

- No active unresolved infection

- No known HIV positivity

- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy

Exclusion criteria:

- Known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus or
temsirolimus) or to its excipients

- Gastrointestinal (GI) disease, condition, or symptoms that may significantly impair
GI function and alter the absorption of everolimus, including any of the following:

- Ulcerative disease

- Uncontrolled nausea

- Vomiting

- Diarrhea

- Malabsorption syndrome

- Other active malignancy or malignancy at ≥ 30% risk for relapse after completion of
therapy, except nonmelanoma skin cancer

- Uncontrolled concurrent illness including, but not limited to, any of the following:

- Ongoing or active infection (e.g., bacterial, viral or fungal)

- Severely impaired lung function

- Uncontrolled diabetes (fasting serum glucose > 1.5 times ULN)

- Liver disease (e.g., cirrhosis, chronic active hepatitis, or chronic persistent
hepatitis)

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit study compliance

- Any underlying medical condition which, in the principal investigator's opinion, will
make the administration of everolimus hazardous OR obscure the interpretation of
adverse events

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since major surgery

- More than 3 months since finasteride

- No prior or concurrent radiotherapy to the prostate gland or pelvis

- No prior hormones (e.g., luteinizing hormone-releasing hormone [LHRH] agonists, LHRH
antagonists, or antiandrogens [e.g., bicalutamide, flutamide, or nilutamide]) and/or
PC-SPES (or PC-x product) or estrogen-containing nutraceuticals

- No prior rapamycin mTOR inhibitor

- No prior small bowel resection that may significantly impair GI function and alter
the absorption of everolimus

- No prior or concurrent immunotherapy, chemotherapy, or other investigational therapy
for prostate cancer

- No other concurrent investigational or commercial agents

- No other concurrent anticancer agents

- No concurrent, chronic treatment with systemic steroids (except inhaled or topical
steroids) or another immunosuppressive agent

- No concurrent live vaccines

- No concurrent strong inhibitors or inducers of the isoenzyme CYP3A administered as
systemic therapy