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

Neoplasms, Prostate Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00470834
• Other study ID #: AVO108943
• Status: Completed
• Phase: Phase 4
• First received: May 7, 2007
• Last updated: August 29, 2013
• Start date: May 2007
• Est. completion date: February 2013

Study information

• Verified date: July 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms, Prostate
• Prostatic Neoplasms

Intervention

Drug:
• dutasteride
0.5mg dutasteride (Investigation Product)
• placebo
making placebo
• bicalutamide
50 mg Casodex or generic equivalent

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Barrie	Ontario
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Greenfield Park	Quebec
Canada	GSK Investigational Site	Laval	Quebec
Canada	GSK Investigational Site	North Bay	Ontario
Canada	GSK Investigational Site	Oakville	Ontario
Canada	GSK Investigational Site	Pointe-Claire	Quebec
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Scarborough	Ontario
Canada	GSK Investigational Site	Sudbury	Ontario
Canada	GSK Investigational Site	Surrey	British Columbia
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Victoria	British Columbia
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Annapolis	Maryland
United States	GSK Investigational Site	Aventura	Florida
United States	GSK Investigational Site	Bala Cynwyd	Pennsylvania
United States	GSK Investigational Site	Chaska	Minnesota
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Concord	North Carolina
United States	GSK Investigational Site	Daytona Beach	Florida
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Evansville	Indiana
United States	GSK Investigational Site	Fort Wayne	Indiana
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Galesburg	Illinois
United States	GSK Investigational Site	Garden City	New York
United States	GSK Investigational Site	Homewood	Alabama
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntsville	Alabama
United States	GSK Investigational Site	Jeffersonville	Indiana
United States	GSK Investigational Site	Lancaster	Pennsylvania
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Manhasset	New York
United States	GSK Investigational Site	Memphis	Tennessee
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Myrtle Beach	South Carolina
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norfork	Virginia
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Overland Park	Kansas
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Bernardino	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Shreveport	Louisiana
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Virginia Beach	Virginia
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Watertown	Massachusetts
United States	GSK Investigational Site	Williamsburg	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Disease Progression	Time to disease progression (PD) is defined as the interval of time between the date of the start of treatment and the date of PD. PD is defined as prostate specific antigen (PSA) progression from Baseline (PSA value is 25% and at least 2 nanograms per milliliter [ng/mL] above Baseline, confirmed by a second PSA value); PSA progression from nadir, without a 50% decrease from Baseline (PSA value is 25% and at least 2 ng/mL above nadir, confirmed by a second PSA value); PSA progression from nadir, with a 50% or more decrease from Baseline (PSA value is 50% and at least 2 ng/mL above nadir, confirmed by a second PSA value); metastatic disease (radiographic evidence of metastatic disease); death due to prostate cancer; or the receipt of post-Baseline rescue medication. PSA confirmation was not required if no subsequent PSA values were available. Participants who did not experience an event were censored at the date of the latest follow-up information.	Interval of time between the date of the start of treatment and the date of disease progression (up to Study Month 42)	No
Secondary	Time to Treatment Failure	Time to treatment failure is defined as the interval of time between the date of the start of treatment and the date of treatment failure. Treatment failure is defined as PSA progression from Baseline (PSA value is 25% and at least 2 ng/mL above Baseline, confirmed by a second PSA value); metastatic disease (radiographic evidence of metastatic disease); death due to prostate cancer; or receipt of post-baseline rescue medications. PSA confirmation was not required if no subsequent PSA values were available. Participants who did not experience an event were censored at the date of the latest follow-up information.	Interval of time between the date of the start of treatment and the date of treatment failure (up to Study Month 42)	No
Secondary	Number of Participants With PSA Response	PSA response is defined as a 50% or greater decrease in PSA from Baseline, confirmed by a second PSA measurement. The time of this response was the date of the first PSA measurement that showed a 50% or greater decrease from the Baseline PSA measurement. PSA confirmation was not required if no subsequent PSA values were available.	Time from Baseline PSA measurement until the first PSA measurement with a 50% or greater reduction in PSA values (up to Study Month 42)	No
Secondary	Change From Baseline in Total PSA at Months 6, 12, 18, 21, and 42	Change from Baseline in total PSA was measured at each scheduled post-baseline visit using a general linear model with effects for treatment and Baseline total PSA. Analysis was done using the last observation carried forward (LOCF) approach, in which missing post-Baseline values were imputed with earlier non-missing values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline and Months 6, 12, 18, 21, and 42	No
Secondary	Number of Participants With Metastatic Disease	Metastatic disease is that evidenced by a radiographic assessment. The time of metastatic disease was the date of radiographic evidence.	Interval of time between the date of the start of treatment and the date of radiographic evidence of metastatic disease (up to Study Month 42)	No