Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter, 2 arm study.

The study population will consist of prostate cancer patients with metastatic bone disease
for whom androgen-deprivation therapy is planned. After stratification based on the
patient's age, performance status, and severity of metastatic disease, the patients will be
randomized at a 1:1 ratio to the following treatment arms:

- Daily oral risedronate combined with androgen deprivation

- Daily oral placebo combined with androgen deprivation

Initial clinical evaluation will be performed during the 2-week screening period. While
patients receive per-protocol treatment, study assessments will be performed every 4 weeks
during the first 3 months, and every 12 weeks thereafter.

Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 2

Life Expectancy: At least 12 weeks

Hematopoietic:

- Absolute neutrophil count (ANC) > 1,000/mm3

- Platelet count > 100,000/mm3

- international normalized ratio (INR) < 1.5 x upper limit of normal unless on
therapeutic anticoagulation

- Partial thromboplastin time (PTT) < 1.5 x upper limit of normal unless on therapeutic
anticoagulation

Hepatic:

- Bilirubin < 1.5 mg/dL

- Alanine transaminase (ALT) < 2.5 x upper limit of normal

Renal:

- Creatinine clearance of > 30 mL/min (by Cockcroft-Gault)

Cardiovascular:

- No significant history of uncontrolled cardiac disease (i.e., uncontrolled
hypertension, unstable angina, and congestive heart failure).

Pulmonary:

- Not specified

Calcium:

- Corrected serum calcium = (4.0 g/dL - actual albumin g/dL)x 0.8 + serum calcium

Inclusion Criteria:

- Histologically or cytologically confirmed adenocarcinoma of the prostate with
metastatic bone disease (by CT, MRI or bone scan) with plans to start or be < 30 days
from beginning androgen deprivation therapy. Patients with lymph node or visceral
metastases only are not eligible

- Patients may receive palliative radiation therapy at the investigators discretion
during the first 4 weeks of beginning protocol therapy.

Exclusion Criteria:

- No neuroendocrine, small cell or transitional cell cancer of the prostate No abnormal
bone metabolism (i.e., Paget's disease, untreated hyperthyroidism, untreated
hyperprolactinemia, untreated Cushing's disease).

- No use of calcitonin within 14 days before being registered for protocol therapy or
any previous use of bisphosphonates.

- No major surgery within 4 weeks of registration to protocol therapy.

- No adjuvant chemotherapy within 6 months of registration to protocol therapy.

- No previous chemotherapy for metastatic disease.

- No hormonal therapy in the adjuvant setting within 12 months of registration to
protocol therapy; previous hormonal therapy must not have exceeded 6 months.

- No prior history of malignancy in the past 5 years with the exception of basal cell
and squamous cell carcinoma of the skin.

- No history of allergy or drug reactions to bisphosphonates.