Clinical trial NCT00470834: Prostate Cancer Study In Men Who Have Failed First-Line Androgen Deprivation Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neoplasms, Prostate
Keywords: prostate cancer
androgen deprivation therapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-05-08
Enrollment: 127
Sex: MALE
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to Disease Progression
timeFrame: Interval of time between the date of the start of treatment and the date of disease progression (up to Study Month 42)
Secondary outcomes:
measure: Time to Treatment Failure
timeFrame: Interval of time between the date of the start of treatment and the date of treatment failure (up to Study Month 42)
measure: Number of Participants With PSA Response
timeFrame: Time from Baseline PSA measurement until the first PSA measurement with a 50% or greater reduction in PSA values (up to Study Month 42)
measure: Change From Baseline in Total PSA at Months 6, 12, 18, 21, and 42
timeFrame: Baseline and Months 6, 12, 18, 21, and 42
measure: Number of Participants With Metastatic Disease
timeFrame: 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)
Other outcomes:
Locations:
city: Homewood
country: United States
facility: GSK Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: GSK Investigational Site
state: Alabama
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: GSK Investigational Site
state: California
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: San Bernardino
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Aventura
country: United States
facility: GSK Investigational Site
state: Florida
city: Daytona Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Galesburg
country: United States
facility: GSK Investigational Site
state: Illinois
city: Evansville
country: United States
facility: GSK Investigational Site
state: Indiana
city: Fort Wayne
country: United States
facility: GSK Investigational Site
state: Indiana
city: Jeffersonville
country: United States
facility: GSK Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Annapolis
country: United States
facility: GSK Investigational Site
state: Maryland
city: Watertown
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Chaska
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Garden City
country: United States
facility: GSK Investigational Site
state: New York
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Concord
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Bala Cynwyd
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Lancaster
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Norfork
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Virginia Beach
country: United States
facility: GSK Investigational Site
state: Virginia
city: Williamsburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Barrie
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Burlington
country: Canada
facility: GSK Investigational Site
state: Ontario
city: North Bay
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Scarborough
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Laval
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: