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