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

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

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 Overview

• Status: Completed
• Conditions: Neoplasms, Prostate
• Intervention / Treatment: Drug: dutasteride; Drug: bicalutamide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 2J6
    • GSK Investigational Site
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • GSK Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1N1
      • GSK Investigational Site
    • Victoria, British Columbia, Canada, V8T 5G1
      • GSK Investigational Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • GSK Investigational Site
    • Burlington, Ontario, Canada, L7S 1V2
      • GSK Investigational Site
    • North Bay, Ontario, Canada, P1B 7K8
      • GSK Investigational Site
    • Oakville, Ontario, Canada, L6H 3P1
      • GSK Investigational Site
    • Scarborough, Ontario, Canada, M1S 4V5
      • GSK Investigational Site
    • Sudbury, Ontario, Canada, P3E 4T3
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M4C 5T2
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M2K 2W1
      • GSK Investigational Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H3
      • GSK Investigational Site
    • Laval, Quebec, Canada, H7G 2E6
      • GSK Investigational Site
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • GSK Investigational Site
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • GSK Investigational Site
    • Huntsville, Alabama, United States, 35801
      • GSK Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • GSK Investigational Site
  • California
    • Anaheim, California, United States, 92801
      • GSK Investigational Site
    • Fresno, California, United States, 93720
      • GSK Investigational Site
    • San Bernardino, California, United States, 92404
      • GSK Investigational Site
    • San Diego, California, United States, 92101
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80211
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • GSK Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • GSK Investigational Site
    • Daytona Beach, Florida, United States, 32114
      • GSK Investigational Site
    • Orlando, Florida, United States, 32803
      • GSK Investigational Site
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • GSK Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47713
      • GSK Investigational Site
    • Fort Wayne, Indiana, United States, 46825
      • GSK Investigational Site
    • Jeffersonville, Indiana, United States, 47130
      • GSK Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • GSK Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • GSK Investigational Site
    • Shreveport, Louisiana, United States, 71106
      • GSK Investigational Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • GSK Investigational Site
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • GSK Investigational Site
  • Minnesota
    • Chaska, Minnesota, United States, 55318
      • GSK Investigational Site
    • Minneapolis, Minnesota, United States, 55455
      • GSK Investigational Site
  • Missouri
    • St. Louis, Missouri, United States, 63136
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • GSK Investigational Site
  • New York
    • Albany, New York, United States, 12208
      • GSK Investigational Site
    • Garden City, New York, United States, 11530
      • GSK Investigational Site
    • Manhasset, New York, United States, 11030
      • GSK Investigational Site
    • New York, New York, United States, 10016
      • GSK Investigational Site
    • Syracuse, New York, United States, 13210
      • GSK Investigational Site
  • North Carolina
    • Concord, North Carolina, United States, 28025
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43214
      • GSK Investigational Site
  • Pennsylvania
    • Bala Cynwyd, Pennsylvania, United States, 19004
      • GSK Investigational Site
    • Lancaster, Pennsylvania, United States, 17604
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • GSK Investigational Site
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • GSK Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77074
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Virginia
    • Norfork, Virginia, United States, 23502
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23235
      • GSK Investigational Site
    • Virginia Beach, Virginia, United States, 23454
      • GSK Investigational Site
    • Williamsburg, Virginia, United States, 23185
      • GSK Investigational Site
  • Washington
    • Seattle, Washington, United States, 98166
      • GSK Investigational Site
    • Seattle, Washington, United States, 98195-6015
      • GSK Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 50 mg bicalutamide and 3.5 mg Dutasteride (IP)	Drug: dutasteride; 0.5mg dutasteride (Investigation Product); Drug: bicalutamide; 50 mg Casodex or generic equivalent
Placebo Comparator: Arm 2; 50 mg bicalutamide and placebo	Drug: bicalutamide; 50 mg Casodex or generic equivalent; Drug: placebo; making placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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
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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: May 7, 2007
• First Submitted That Met QC Criteria: May 7, 2007
• First Posted (Estimate): May 8, 2007

Study Record Updates

• Last Update Posted (Actual): February 27, 2017
• Last Update Submitted That Met QC Criteria: January 12, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: prostate cancer; androgen deprivation therapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; Androgen Antagonists; 5-alpha Reductase Inhibitors; Bicalutamide; Dutasteride
• Other Study ID Numbers: AVO108943

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: AVO108943
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register