RAD001 and Bicalutamide for Androgen Independent Prostate Cancer

The goal of this clinical trial is to learn if the study drug RAD001 in combination with Bicalutamide can slow the growth of prostate cancer. The safety of RAD001 given together with Bicalutamide will also be studied. RAD001 has been shown to kill prostate cancer cells. In addition, several hundred kidney and heart transplant patients have been treated with the same main ingredient as in RAD001 for many years.

• Participants will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time participants will take RAD001 and bicalutamide orally, once per day. RAD001 will be provided from the research pharmacy at the hospital and a prescription will be given for bicalutamide to obtain from a local pharmacy.
• A history, physical exam, and blood tests will be performed every four weeks. An assessment of the tumor by Chest CT scan, chest x-ray, bone scan, and abdomen/pelvis CT or MRI will be performed every 12 weeks.

• Drug: RAD001
  Taken orally once daily
• Drug: Bicalutamide
  Taken orally once daily

Inclusion Criteria:

• 18 years of age or older
• Histologically documented prostate cancer
• Castration resistant prostate cancer defined as two rising PSAs on castration therapy
• Baseline PSA of 2ns/mL or greater
• Testosterone of 50ng/mL or less
• Patients on LHRH agonist/antagonist must continue therapy at the recommended dosing intervals
• Prior bicalutamide is allowed as long as treatment was for 6 months or longer
• Metastatic disease is not required
• Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
• ECOG Performance Status equal to or less than 2
• Adequate bone marrow and liver function as outlined by parameters in the protocol

Exclusion Criteria:

• Prior treatment with any investigational drug within the preceding 4 weeks
• Prior treatment with an mTOR inhibitor
• Fasting lipids over the parameters outlined in the protocol
• Chronic treatment with systemic steroids or another immunosuppressive agent
• Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated or basal squamous cell carcinomas of the skin
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)
• Men able to conceive and unwilling to practice an effective method of birth control
• Known hypersensitivity to RAD001 or other rapamycins or to its excipients
• History of noncompliance to medical regimens

• Beth Israel Deaconess Medical Center
• Novartis Pharmaceuticals