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
  Purpose

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).


Condition Intervention Phase
Prostate Cancer
Drug: Dutasteride
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Dutasteride on Androgen-Response Gene Expression During the Tumor Regrowth Phase of Intermittent Androgen Ablation Therapy in Patients With Advanced Prostate Cancer

Resource links provided by NLM:


Further study details as provided by NorthShore University HealthSystem Research Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 21
Study Start Date: March 2007
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Dutasteride
0.5 mg capsule given orally on daily basis
Other Name: Avodart
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
Drug: Placebo
Identical placebo
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668642

Locations
United States, Illinois
University of Chicago Hospitals and Clinics
Chicago, Illinois, United States, 60637
Northwestern University Medical Center
Chicago, Illinois, United States, 60611
NorthShore University HealthSystem
Evanston, Illinois, United States, 60201
Sponsors and Collaborators
NorthShore University HealthSystem Research Institute
University of Chicago
Northwestern University
Investigators
Principal Investigator: Daniel H Shevrin, MD NorthShore University HealthSystem
  More Information

No publications provided

Responsible Party: Daniel Shevrin, MD, Principal Investigator, Division of Hematology/Oncology, NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier: NCT00668642     History of Changes
Other Study ID Numbers: EH07-109
Study First Received: April 28, 2008
Last Updated: February 13, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Dutasteride
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014