Safety Study & Effectiveness of Docetaxel With RAD001 and Bevacizumab in Men With Advanced Prostate Cancer

Inclusion Criteria:

* Age ≥ 18 years.
* Signed informed consent
* ECOG performance status: 0-2
* Histologically documented adenocarcinoma of the prostate
* Progressive disease despite androgen deprivation therapy. Progressive disease is defined as any one of the following:
* Measurable Disease: Objective evidence of increase \> 20% in the sum of the longest diameters of target lesions from the time of maximal regression or the appearance of one or more new lesions (Modified RECIST Criteria)
* Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer
* PSA Progression: An elevated PSA (≥ 5 ng/ml) which has risen serially from baseline on two occasions each at least one week apart
* At least 4 weeks since any other hormonal therapy. Flutamide and megestrol acetate (any dose) must be discontinued at least 4 weeks prior to initiating treatment. Bicalutamide or nilutamide must be discontinued at least 6 weeks prior to initiating treatment. If improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above. Androgen suppression should be continued
* ≥ 4 weeks since major surgery and fully recovered
* ≥ 8 weeks since high risk surgery and fully recovered
* ≥ 4 weeks since any prior radiation and fully recovered
* ≥ 6 weeks since the last dose of bone targeted radiopharmaceutical
* Men of child-bearing potential are required to use an effective means of contraception
* Required Initial Laboratory Values:

  * ANC ≥ 1500/µL
  * Platelet count ≥ 100,000/µL
  * Creatinine ≤ 1.5 x ULN
  * Bilirubin ≤ 1.5 x ULN
  * AST ≤ 1.5 x ULN
  * Urine protein to creatinine ratio \< 1.0
  * Serum Testosterone ≤ 50 ng/dL (For patients who have not had bilateral orchiectomy.)

Exclusion Criteria:

* Prior treatment with cytotoxic chemotherapy for metastatic disease
* Prior treatment with anti-angiogenic agents, including thalidomide and bevacizumab
* Prior treatment with any investigational drug within 4 weeks of initiating treatment
* Prior treatment with an mTor inhibitor
* Chronic treatment with systemic steroids or another immunosuppressive agent
* Known history of HIV seropositivity
* Known brain metastases (brain imaging is not required)
* Congestive heart failure
* Uncontrolled hypertension. Patients with history of hypertension must be well controlled (\< 150/100) on a regimen of anti-hypertensive therapy
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
* Active bleeding diathesis or on oral anti-vitamin K medications (except low dose coumarin)
* Arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), at any time
* History of unstable angina or angina requiring surgical or medical intervention in the past 12 months, or myocardial infarction (MI)
* Patients with clinically significant peripheral artery disease or any other arterial thrombotic event
* Significant vascular disease
* Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study
* Proteinuria at screening as demonstrated by either
* Urine protein:creatinine (UPC) ratio ≥ 1.0 OR
* Urine dipstick for proteinuria ≥ 2+
* Serious or non-healing wound, ulcer or bone fracture
* Peripheral neuropathy ≥ grade 2
* Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* Herbal medications and food supplements must be discontinued before registration. Patients may continue on daily vitamins and calcium supplements
* History of noncompliance to medical regimens
* Unwilling to or unable to comply with the protocol