Clinical trial NCT00363311: Assessment Of Dutasteride (AVODART) In Extending The Time To Progression Of Low-Risk, Localized Prostate Cancer In Men
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Dutasteride in Extending the Time to Progression of Low-Risk, Localized Prostate Cancer in Men Who Are Candidates for or Undergoing Expectant Management
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neoplasms, Prostate
Keywords: Dutasteride Prostate Cancer Expectant management REDEEM
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-08-15
Enrollment: 302
Sex: MALE
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the effect of dutasteride on the inhibition of low-risk, localized prostate cancer progression in men who would otherwise receive no active therapy (expectant management).


Eligibility criteria: Inclusion criteria:

* Must be male ≥48 and ≤82 years of age
* Have biopsy proven, low-risk, localized prostate cancer and active in expectant management not more than 14 months. \[For the purposes of assessing subject eligibility a diagnostic biopsy must have included at least 10 cores, (\< 4 cores positive and \<50% of any one core positive) and must have been obtained within 8 months of screening\]. If a saturation biopsy was performed (20 or more cores obtained) 2-3 cores are to be positive for prostate cancer and with \<50% of any one core positive. Initial diagnosis of T1a/T1b obtained during a Transrectal ultrasound (TURP) is not allowed.
* Gleason score ≤6 \[Gleason pattern 4 or above must not be present on any biopsy (initial or entry)\]
* Clinical stage T1c-T2a
* Serum Prostate Specific Antigen (PSA) ≤11ng/mL. If the screening PSA value from the central laboratory is greater than 11ng/ml, one PSA retest is allowed through the central laboratory
* A life expectancy greater than five years.
* Able to swallow and retain oral medication
* Able and willing to participate in the full 3 years of the study
* Able to read and write (health outcomes questionnaires are self-administered), understand instructions related to study procedures and give written informed consent.

Exclusion criteria:

* Subject has ever been treated for prostate cancer with any of the following:
* Radiotherapy (external beam or brachytherapy)
* Chemotherapy
* Hormonal therapy (e.g., megestrol, medroxyprogesterone, cyproterone, diethylstilbestrol (DES)
* Oral glucocorticoids
* Gonadotropin-releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin)
* Glucocorticoids, except inhaled or topical, are not permitted within 3 months prior to visit one
* Current and/or previous use of the following medications:
* Finasteride (Proscar, Propecia), or Dutasteride (GI198745, AVODART) exposure within 6 months prior to study entry are excluded.
* Any other investigational 5α-reductase inhibitors within the past 12 months.
* Anabolic steroids (subject must discontinued for 6 months prior to study entry to be eligible)
* Drugs with antiandrogenic properties within the past 6 months (e.g,. spironolactone, flutamide, bicalutamide, \*cimetidine, \*ketoconazole, metronidazole, progestational agents) NOTE: Use of dietary and herbal supplements (e.g., selenium, Vitamin E, saw palmetto) during the study is discouraged but not prohibited. All dietary and herbal supplement usage will be recorded in the case report form (CRF).

  \*The use of cimetidine is permitted prior to study entry. The use of topical ketoconazole is permitted prior to and during the study.
* Prostate volume \>80 cc
* Subject has had prior prostatic surgery including Transurethral needle ablation of the prostate (TUNA), TURP, Transurethral incision of the prostate (TUIP), laser treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation within 3 months of enrolment
* Severe Benign Prostatic Hyperplasia (BPH) symptoms as manifested by International Prostate Symptom Score (IPSS) symptom score (calculated using the first 7 questions only) of ≥25 or \>20 if already on alpha blocker therapy.
* 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 2 times the upper limit of normal for alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], or alkaline phosphatase \[ALP\]); or bilirubin \>1.5 times the upper limit of normal.
* Serum creatinine \>1.5 times the upper limit of normal.
* History of another malignancy within five years that could affect the diagnosis of prostate cancer.
* 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 5α-reductase inhibitor or to any drug chemically related to dutasteride.

Primary outcomes:
measure: Number of Participants With Prostate Cancer (PCa) Progression [Restricted Crude Rate Analysis: Number of Participants With PCa Divided by Number of Participants in the Intent-to-Treat (ITT) Population Who Had >=1 Post-baseline Biopsy or Had a Progression
timeFrame: Year 1.5 and Overall (Years 0-3)
Secondary outcomes:
measure: Number of Participants With Therapeutic Progression
timeFrame: Year 1.5 and Overall (Years 0-3)
measure: Number of Participants With Pathologic Progression
timeFrame: Year 1.5 and Overall (Years 0-3)
measure: Participants With at Least One Post-baseline Biopsy With the Indicated Prostate Cancer (PCa) Diagnosis
timeFrame: Baseline to Month 18
measure: Participants With at Least One Post-baseline Biopsy With the Indicated Prostate Cancer (PCa) Diagnosis for Their Final Biopsy
timeFrame: Years 0-3
measure: Number of Cancer-positive Cores in a 12-core Biopsy
timeFrame: Baseline, Year 1.5, Year 3, Years 0-3 (Final biopsy)
measure: Change From Baseline in the Number of Cancer-positive Cores in a 12-core Biopsy at Years 1.5, 3, and 0-3
timeFrame: Baseline, Year 1.5, Year 3, Years 0-3 (Final biopsy)
measure: Mean Percentage of Cancer-positive Cores in a 12-core Biopsy
timeFrame: Baseline, Year 1.5, Year 3, Years 0-3 (Final biopsy)
measure: Change From Baseline in the Percentage of Cancer-positive Cores in a 12-core Biopsy at Years 1.5, 3, and 0-3
timeFrame: Baseline, Year 1.5, Year 3, Years 0-3 (Final biopsy)
measure: Cumulative Length of Cancer Tumor Core
timeFrame: Baseline, Year 1.5, Year 3, Years 0-3 (Final biopsy)
measure: Change From Baseline in the Cumulative Length of Cancer Tumor Core at Years 1.5, 3, and 0-3
timeFrame: Baseline, Year 1.5, Year 3, Years 0-3 (Final biopsy)
measure: Number of Participants With the Indicated Change From Baseline in Gleason Score (GS) on Repeat Biopsy at Year 1.5
timeFrame: Year 1.5
measure: Number of Participants With the Indicated Change From Baseline in Gleason Score on Repeat Biopsy at Years 0-3
timeFrame: Years 0-3 (Final Biopsy)
measure: Number of Participants With the Indicated Total Gleason Score
timeFrame: Years 0-3 (Final Biopsy)
measure: Number of Biopsies With the Indicated Clinical Tumor Stage at Baseline
timeFrame: Baseline
measure: Number of Post-baseline Biopsies With the Indicated Change From Baseline in Clinical Stage
timeFrame: Months 0-18
measure: Prostate Volume (PV) LOCF
timeFrame: Baseline and Years 1.5 and 3
measure: Change From Baseline in Prostate Volume at Years 1.5 and 3
timeFrame: Baseline and Years 1.5 and 3
measure: Percent Change From Baseline in Prostate Volume at Years 1.5 and 3
timeFrame: Baseline and Years 1.5 and 3
measure: Total Memorial Anxiety Scale Scores for Prostate Cancer (MAX-PC)
timeFrame: Baseline and Month 3, 6, 12, 18, and 36
measure: Change From Baseline in Total Memorial Anxiety Scale Scores for Prostate Cancer (MAX-PC) LOCF
timeFrame: Baseline and Months 3, 6, 12, 18, and 36
measure: Total MAX-PC Anxiety Subscale Score Related to PSA Testing
timeFrame: Baseline and Months 3, 6, 12, 18, and 36
measure: Change From Baseline in MAX-PC Anxiety Subscale Score Related to PSA Testing (LOCF)
timeFrame: Baseline and Months 3, 6, 12, 18, and 36
measure: Total MAX-PC Fear of Recurrence Subscale Score
timeFrame: Baseline and Months 3, 6, 12, 18, and 36
measure: Change From Baseline in MAX-PC Fear of Recurrence Subscale Score (LOCF)
timeFrame: Baseline and Months 3, 6, 12, 18, and 36
measure: Total Functional Assessment of Cancer Therapy Scale, Prostate Module (FACT-P) Score
timeFrame: Baseline and Months 18 and 36
measure: Change From Baseline in Total FACT-P Score (LOCF)
timeFrame: Baseline and Months 18 and 36
measure: Percent Change From Baseline in Total FACT-P Score (LOCF)
timeFrame: Baseline and Months 18 and 36
measure: Change From Baseline in FACT-P Physical Well-Being Subscale Score (LOCF)
timeFrame: Baseline and Months 18 and 36
measure: Change From Baseline in FACT-P Social Well-Being Subscale Score (LOCF)
timeFrame: Baseline and Months 18 and 36
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Beverly Hills
country: United States
facility: GSK Investigational Site
state: California
city: Laguna Hills
country: United States
facility: GSK Investigational Site
state: California
city: Mission Hills
country: United States
facility: GSK Investigational Site
state: California
city: Modesto
country: United States
facility: GSK Investigational Site
state: California
city: San Bernardino
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Englewood
country: United States
facility: GSK Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: GSK Investigational Site
state: Colorado
city: New Britain
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Trumbull
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Largo
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Roswell
country: United States
facility: GSK Investigational Site
state: Georgia
city: Coeur D'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Melrose Park
country: United States
facility: GSK Investigational Site
state: Illinois
city: Fort Wayne
country: United States
facility: GSK Investigational Site
state: Indiana
city: Newburgh
country: United States
facility: GSK Investigational Site
state: Indiana
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Shreveport
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Annapolis
country: United States
facility: GSK Investigational Site
state: Maryland
city: Greenbelt
country: United States
facility: GSK Investigational Site
state: Maryland
city: Watertown
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: St. Cloud
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: GSK Investigational Site
state: Mississippi
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Marlton
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Albany
country: United States
facility: GSK Investigational Site
state: New York
city: Elmont
country: United States
facility: GSK Investigational Site
state: New York
city: Garden City
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Orchard Park
country: United States
facility: GSK Investigational Site
state: New York
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Springfield
country: United States
facility: GSK Investigational Site
state: Oregon
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: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Temple
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
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: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Surrey
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Fredericton
country: Canada
facility: GSK Investigational Site
state: New Brunswick
city: Barrie
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Brantford
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Burlington
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Burlington
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Guelph
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Kitchener
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: Toronto
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: Chicoutimi
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Laval
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012 Mar 24;379(9821):1103-11. doi: 10.1016/S0140-6736(11)61619-X. Epub 2012 Jan 24.
citation: Moreira DM, Fleshner NE, Freedland SJ. Baseline Perineural Invasion is Associated with Shorter Time to Progression in Men with Prostate Cancer Undergoing Active Surveillance: Results from the REDEEM Study. J Urol. 2015 Nov;194(5):1258-63. doi: 10.1016/j.juro.2015.04.113. Epub 2015 May 16.