Assessment Of Dutasteride (AVODART) In Extending The Time To Progression Of Low-Risk, Localized Prostate Cancer In Men

GlaxoSmithKline302 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

302

Conditions

Neoplasms, Prostate

Interventions

DutasterideDRUG

Dutasteride 0.5mg

Matching placeboDRUG

Matching placebo

Eligibility

Sex: MALEMin age: 50 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Locations (82)

Outcomes

Primary Outcomes

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

PC progression (prog.) was defined as the earliest occurrence of primary therapy, also referred to as therapeutic prog., for PC (prostatectomy/radiation/hormonal therapy); or pathological prog., defined as 1 of the following: \>=4 cores involved; \>=50% of any 1 core involved; or a Gleason pattern of \>=4 as a result of any on-study/for-cause biopsy. Primary Gleason grade is assigned to the most common tumor pattern; a second grade to the next most common tumor pattern. The two grades are added together to get a score. Gleason grade= 1-5; Gleason score=2-10; 5 and 10 indicate worst prognosis.

Time frame: Year 1.5 and Overall (Years 0-3)

Secondary Outcomes

Number of Participants With Therapeutic Progression

Primary therapy, also referred to as therapeutic progression, for prostate cancer can be one of the following: prostatectomy, radiation, or hormonal therapy.

Time frame: Year 1.5 and Overall (Years 0-3)

Number of Participants With Pathologic Progression

Pathological progression is defined as one of the following: \>=4 cores involved; \>=50% of any 1 core involved; or a Gleason pattern of \>=4 as a result of any on-study/for-cause biopsy. The 2005 International Society of Urological Pathologists recommendations for Gleason scoring (GS) were used to grade tumors. A primary grade is assigned to the most common tumor pattern, and a second grade to the next most common tumor pattern. The two grades are added together to get a GS. The Gleason grade=1-5, with 5 having the worst prognosis. The Gleason score=2-10, with 10 having the worst prognosis.

Time frame: Year 1.5 and Overall (Years 0-3)

Participants With at Least One Post-baseline Biopsy With the Indicated Prostate Cancer (PCa) Diagnosis

All participants were required by protocol to undergo a transrectal ultrasound (TRUS)-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. If a for-cause biopsy occurred within 6 months prior to the protocol-mandated biopsy, the biopsy was counted as the protocol-mandated biopsy. All biopsies were reviewed and analyzed by a central pathologist.

Data from ClinicalTrials.gov

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GSK Investigational Site

Little Rock, Arkansas, United States

GSK Investigational Site

Beverly Hills, California, United States

GSK Investigational Site

Laguna Hills, California, United States

GSK Investigational Site

Mission Hills, California, United States

GSK Investigational Site

Modesto, California, United States

GSK Investigational Site

San Bernardino, California, United States

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Englewood, Colorado, United States

GSK Investigational Site

Wheat Ridge, Colorado, United States

GSK Investigational Site

New Britain, Connecticut, United States

...and 72 more locations

Time frame: Baseline to Month 18

Participants With at Least One Post-baseline Biopsy With the Indicated Prostate Cancer (PCa) Diagnosis for Their Final Biopsy

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. If a for-cause biopsy occurred within 6 months prior to the protocol-mandated biopsy, the biopsy was counted as the protocol-mandated biopsy. The final biopsy is defined as the latest post-baseline biopsy for which the results are available from the central pathology laboratory.

Time frame: Years 0-3

Number of Cancer-positive Cores in a 12-core Biopsy

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist. . The final biopsy is defined as the latest post-baseline biopsy for which the results are available from the central pathology laboratory.