Effect of Dutasteride on Androgen-Response Gene Expression in Patients With Advanced Prostate Cancer

This study has been completed.
Sponsor:
Collaborators:
University of Chicago
Northwestern University
Information provided by (Responsible Party):
Daniel Shevrin, MD, NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier:
NCT00668642
First received: April 28, 2008
Last updated: February 13, 2014
Last verified: February 2014

April 28, 2008
February 13, 2014
March 2007
May 2013   (final data collection date for primary outcome measure)
Level of U19 gene expression in tumor from prostate gland. [ Time Frame: Biopsy of prostate tumor during off-phase of intermittent androgen ablation therapy ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00668642 on ClinicalTrials.gov Archive Site
Determination of PSA doubling time during off-phase of treatment [ Time Frame: Montly PSA measures during off-phase of treatment ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Effect of Dutasteride on Androgen-Response Gene Expression in Patients With Advanced Prostate Cancer
Effect of Dutasteride on Androgen-Response Gene Expression During the Tumor Regrowth Phase of Intermittent Androgen Ablation Therapy in Patients With Advanced Prostate Cancer

The purpose of this study is to determine if the drug dutasteride increases expression of genes that slow the growth of prostate cancer during treatment with intermittent androgen ablation therapy (hormone therapy).

We have shown in a murine model of treatment with intermittent androgen ablation therapy of prostate cancer that when dutasteride is given during the regrowth phase (off-phase) of intermittent therapy, that tumor growth is inhibited and that survival is improved. We have also shown that testosterone is a more potent inducer of certain tumor suppressor androgen response genes than dihydrotestosterone. In this murine model, we showed that use of a 5-alpha reductase inhibitor (dutasteride) resulted in significant hyperinduction of the U19 tumor suppressor androgen response gene during the regrowth phase of treatment. In the current clinical trial, we will determine if use of dutasteride in men with advanced prostate cancer during the off-phase of intermittent androgen ablation therapy will also result in hyperinduction of these tumor suppressor androgen response genes. Gene expression will be measured in tumor tissue obtained by prostate biopsies during the off-phase when the testosterone level has normalized. PSA levels will also be measured to determine the PSA doubling time during the off-phase to determine the effect of dutasteride on PSA kinetics.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Prostate Cancer
  • Drug: Dutasteride
    0.5 mg capsule given orally on daily basis
    Other Name: Avodart
  • Drug: Placebo
    Identical placebo
    Other Name: Placebo
  • Experimental: A: Dutasteride During First Off-Cycle
    Arm A patients received dutasteride (0.5 mg/day) during the first off-cycle and received placebo during the second off-cycle
    Intervention: Drug: Dutasteride
  • Placebo Comparator: B: Placebo During First Off-Cycle
    Arm B patients received placebo during the first off-cycle and received dutasteride (0.5 mg/day) during the second off-cycle
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
May 2013
May 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically proven prostate cancer
  • Patients are hormone-naive
  • Patients either to begin androgen ablation therapy with LHRH agonist or already receiving therapy with LHRH agonist
  • Advanced prostate cancer with either positive pelvic nodes or bone/visceral metastasis
  • Must have an intact prostate (no previous surgery or XRT)
  • ECOG performance status 0-2
  • Recovery from any major infection or surgical procedure
  • Signed informed consent

Exclusion Criteria:

  • Known intolerance or allergy to dutasteride
  • Concomitant chemotherapy, biologic therapy, or XRT to prostate
  • Bilateral orchiectomy
  • Prior malignancy within 5 years of registration
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00668642
EH07-109
Yes
Daniel Shevrin, MD, NorthShore University HealthSystem Research Institute
NorthShore University HealthSystem Research Institute
  • University of Chicago
  • Northwestern University
Principal Investigator: Daniel H Shevrin, MD NorthShore University HealthSystem
NorthShore University HealthSystem Research Institute
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP