The purpose of this study is to determine the biochemical response rate (PSA) to single agent RAD001 in patients with metastatic hormone-refractory prostate cancer (HRPC).

This is a single center, Phase II study of RAD001 in men with HRPC. The study design is a straight forward, two-stage design with tumor biopsies scheduled at screening and again at 4 weeks. FLT-PET scans are performed at screening and again at day 28, following initiation of treatment in the first 10 patients. Patients are assessed for adverse events every two weeks for the first month and monthly thereafter. Patients are assessed for response by PSA every 4 weeks and when applicable, for objective response every 2 months. If 4 or more responses are seen in the first 39 patients then the study will expand to 60 patients.

Inclusion Criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the prostate

• Clinical or radiographic evidence of metastatic disease

• ADT using LHRH agonist (eg leuprolide, goserelin) must continue on therapy. However, ketoconazole, estrogens, and all other forms of hormonal manipulation are not permitted on study.

• Evidence of disease progression on ADT as evidenced by:

  • 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, or
  • Radiographic evidence of disease progression defined by RECIST criteria and compared to prior studies on ADT.

• A minimum of 6 weeks has elapsed off of anti-androgen therapy without withdrawal response.

• A minimum of 4 weeks from any prior radiation therapy, surgery, chemotherapy or other investigational agent

• Biopsies will not be performed if platelet counts < 75,000/ ul, PTT, PT or INR > 1.4 times control

• Patients must have normal organ and marrow function as defined below:

• hemoglobin > 9.0g/dL

• absolute neutrophil count > 1,500/μl

• platelets > 100,000/μl

• total bilirubin < 1.5 X upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) < 2.5 X ULN

• creatinine < 1.5 X ULN

• total fasting cholesterol < 350

• total triglycerides < 300

• Patients on antilipid therapy may participate in this study.

• Age > 18 years

• ECOG performance status 0 or 1

• Ability to swallow and retain oral medication

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• History of solid organ or stem cell transplantation
• Also, no current use of chronic immunosuppressive therapy is allowed
• Patients with known brain metastases (or history of brain metastases)
• History of HIV, hepatitis B, or hepatitis C infection
• Patients who have received investigational, biologic, hormonal (other than ADT), immunotherapy, or chemotherapy less than 4 weeks prior to entry on this study or have not recovered from the toxic effects of such therapy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), symptomatic congestive heart failure (NYHC III or greater), unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT or any VT), or psychiatric illness/social situations that would limit compliance with study requirements
• History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs.
• Any unresolved bowel obstruction or diarrhea

3 years

data were collected in Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and converted to version 4.0 for Clinicaltrials.gov entry