Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

INCLUSION CRITERIA

   - Histologically-confirmed adenocarcinoma of the prostate, characterized as symptomatic
   castration-resistant prostate cancer (CRPC)

   - Serum PSA ≥ 2 ng/mL

   - Rising PSA on 3 consecutive occasions at least 1 week apart (not limited to the 30-day
   screening period)

   - Failure of bilateral orchiectomy and/or therapy with an LHRH agonist and bicalutamide

   - Castrate level of testosterone (< 50 ng/dL)

   - Currently being treated with bicalutamide

   - No prior antiandrogen therapy except bicalutamide

   - Age ≥ 18 years

   - Life expectancy > 6 months

   - Performance status

      - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

      - OR

      - Karnofsky performance status ≥ 80%

   - Ability to understand and the willingness to sign a written informed consent

EXCLUSION CRITERIA

   - Radiotherapy for prostate cancer within 28 days prior to Day 1, except single-fraction
   radiotherapy for pain control

   - Prior treatment with mTOR inhibitors

   - Prior treatment with chemotherapy for prostate cancer

   - Symptomatic bone metastases (ie, asymptomatic bone metastases are eligible)

   - Visceral metastases

   - Absolute neutrophil count (ANC) < 1500/uL

   - Platelet count ≤ 100 x 10e9/L

   - Total bilirubin ≥ 1.5 x Upper Limit of Normal (ULN)

   - Alkaline phosphatase > 2.5 x ULN

   - AST > 2.5 x ULN

   - ALT > 2. 5x ULN

   - Serum creatinine > 2.0 mg/dL

   - Hemoglobin < 9 g/dL

   - Men with reproductive potential who do not agree to use an accepted and effective
   method of contraception during the study treatment period and for at least 3 months
   after completion of the study treatment

   - History of other malignancies within 5 years except for tumors with a negligible risk
   for metastasis or death, such as adequately-controlled basal cell carcinoma,
   squamous-cell carcinoma of the skin, or early-stage bladder cancer

   - Participation in another experimental drug study either planned or within 4 weeks of
   the first study treatment

   - Persistent Grade ≥ 1 AEs due to prior drug therapy, including investigational drugs,
   administered more than 14 days before study enrollment

   - Previously treated or other known brain metastases

   - Ongoing or active infection

   - Symptomatic congestive heart failure, New York Heart Association Grade II or greater

   - Unstable angina pectoris

   - Cardiac arrhythmia

   - Significant vascular disease (eg, aortic aneurysm, aortic dissection)

   - Symptomatic peripheral vascular disease

   - Psychiatric illness/social situations that would limit compliance with study
   requirements

   - Other uncontrolled intercurrent illness

   - Known to be positive for the human immunodeficiency virus (HIV) infection and
   receiving antiretroviral therapies (HIV positive not requiring antiretroviral therapy
   iseligible if all other entry criteria are meet)

   - Inability to comply with study and/or follow-up procedures