Official Title: “A Randomized Double-Blind Parallel Group Study Comparing Casodex 50mg Plus Placebo to Casodex 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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2009

Intervention(s) in this Clinical Trial

• Drug: dutasteride

Primary Measures

• Time to disease progression with up to 18 months of treatment PSA progression monitored by monthly PSAs

Secondary Measures

• Time to treatment failure with up to 18 months of treatment by PSA progression form baseline or evidence of metastatic disease
• Percentage of subjects having metastatic disease after up to 18 months of treatment
• Time to Treatment Failure for subjects with up to 18 months of treatment - summarized in the table below.
• Change in PSA value from baseline during up to 18 months of treatment
• Time to disease progression, time to treatment failure, percentage of subjects having PSA response, change in PSA values from baseline,
• and percentage of subjects having metastatic disease for subjects with up to 42 months of treatment (including the two-year extension phase).

Inclusion criteria:

• Men ≥40 and ≤85 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.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: GlaxoSmithKline

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials, MD Study Director GlaxoSmithKline  

Overall Contact: US GSK Clinical Trials Call Center 877-379-3718 

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00470834

Study ID Number: AVO108943

ClinicalTrials.gov Identifier: NCT00470834

Health Authority: United States: Food and Drug Administration