Everolimus, Bicalutamide, and Leuprolide Acetate in Treating Patients Undergoing Radiation Therapy For High-Risk Locally Advanced Prostate Cancer

OBJECTIVES:

Primary

• To assess acute and late toxicities in patients with high-risk, locally advanced prostate cancer.

Secondary

• To assess the biochemical-free survival of these patients.
• To assess metastasis-free survival of these patients.
• To assess the overall survival of these patients.
• To assess the molecular characteristics of the tumor before treatment and correlate with outcomes.

OUTLINE: This is a dose-escalation study of everolimus.

Patients undergo radiotherapy to the prostate and seminal vesicles once daily, 5 days a week, for 7.5 weeks.

Beginning the week before radiotherapy, patients receive oral bicalutamide once daily for 1 month and oral everolimus twice daily for 8.5 weeks. Beginning on the first week of radiotherapy, patients receive leuprolide acetate subcutaneously every 3 months for 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of high-risk, locally advanced prostate cancer meeting ≥ 1 of the following criteria:

• Clinical stage ≥ T3
• Gleason score ≥ 8
• PSA ≥ 20 ng/mL
• Previously untreated disease
• Non-metastatic disease as assessed by bone scan and CT scan of the thorax and abdomen
• Negative pelvic lymph nodes as proven by pathological analysis

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• WBC ≥ 3.5 x 10^9/L
• ANC ≥ 1.5 x 10^9/L
• Platelets normal
• Hemoglobin > 10 g/dL
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Albumin ≥ 3 g/dL
• Serum transaminases activity ≤ 2.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Covered by national health insurance
• No history of previous malignant disease, except for adequately treated basal cell carcinoma of the skin
• No ≥ grade 3 hypercholesterolemia/hypertriglyceridemia or ≥ grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment, if given)
• No uncontrolled infection
• No dysphagia or intestinal malabsorption
• No other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes mellitus, uncontrolled cardiac disease [unstable angina], uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past six months, chronic liver or renal disease, and active upper gastrointestinal tract ulceration)
• No history of noncompliance to medical regimens
• No known hypersensitivity to everolimus, sirolimus (rapamycin), or temsirolimus
• No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study treatment and follow-up schedule

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 30 days since prior investigational drugs
• More than 10 days since prior and no concurrent treatment with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A