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