Prostate Cancer Study In Men Who Have Failed First-Line Androgen Deprivation Therapy

A Randomized Double-Blind Parallel Group Study Comparing Casodex (or Generic Equivalent) 50mg Plus Placebo to Casodex (or Generic Equivalent) 50mg Plus Dutasteride 3.5mg Administered for 18 Months to Men With Prostate Cancer Who Have Failed First-Line Androgen Deprivation Therapy (Assessed by Rising PSA) Followed by a Two-Year Extension Phase

Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT) the male hormone that leads to benign prostate growth. By blocking the conversion of testosterone to DHT, dutasteride could allow bicalutamide to be a more effective anti-androgen thus prolonging bicalutamide's efficacy.

Inclusion criteria:

• Men ≥40 and ≤90 years of age
• Must have asymptomatic prostate cancer that has progressed during androgen deprivation therapy (rising PSA). PSA progression must have occurred after first-line treatment with GnRH analogues ( e.g. leuprolide, goserelin) or orchiectomy. PSA progression is defined by three rises in PSA each measured at least 4 weeks apart within the previous year.
• Serum PSA ≥2 and ≤20ng/ml from central laboratory. One PSA retest from central laboratory is allowed if the value is <2 or >20ng/ml; or if the PSA value is not consistent with the previous rising PSA values that determined progression while on a GnRH analogue.
• Serum Testosterone <50ng/ml from central laboratory.
• Non-metastatic prostate cancer as confirmed on prior bone scan performed within 8 weeks of screening.
• Expected survival ≥ 2 years
• ECOG Performance status 0, 1, or 2

Exclusion criteria:

• Additional hormonal therapy (excluding the current use of a GnRH analogue) within the past 6 months of:

• Estrogens (e.g. megestrol, medroxyprogesterone, cyproterone, DES)

• Drugs with antiandrogenic properties (e.g., spironolactone if >50mg/day, flutamide, bicalutamide*, ketoconazole**, progestational agents)

  *The use of an antiandrogen during GnRH analogue induction for <6 weeks is acceptable, but none within the 3 months prior to study entry.

  **The use of topical ketoconazole is permitted prior to and during the study. NOTE: Use of dietary and herbal supplements (e.g., selenium, Vitamin E, saw palmetto), excluding daily vitamins, during the study is discouraged, but not prohibited. All dietary and herbal supplement usage will be recorded in the eCRF.

• Treatment with oral glucocorticoids during the 3 months prior to randomization or expectation of their use during the study.

• Prior chemotherapy for prostate cancer. (prior prostatectomy or radiotherapy to the prostate are allowed)

• Prostate surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and cryosurgical ablation within 2 months prior to enrollment.

• Current and/or previous use of the following medications:

• Finasteride (Proscar, Propecia), or Dutasteride (GI198745, AVODART) exposure within 6 months prior to study entry

• Anabolic steroids (within 6 months prior to study entry)

• Participation in any investigational or marketed drug trial within the 30 days prior to the first dose of study drug or anytime during the study period.

• Any unstable serious co-existing medical condition(s) including but not limited to myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit; uncontrolled diabetes; or peptic ulcer disease which is uncontrolled by medical management.

• Abnormal liver function test greater than 1.5 times the upper limit of normal for alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] or bilirubin.

• Serum creatinine >2.0 times the upper limit of normal.

• History of another malignancy within five years that could affect the treatment of prostate cancer or survival of the subject.

• History or current evidence of drug or alcohol abuse within the last 12 months.

• History of any illness (including psychiatric) that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject.

• Known hypersensitivity to any 5 alpha-reductase inhibitor or to any drug chemically related to dutasteride.