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

Sponsor:	NorthShore University HealthSystem Research Institute
Collaborators:	University of Chicago Northwestern University
Information provided by:	NorthShore University HealthSystem Research Institute
ClinicalTrials.gov Identifier:	NCT00668642

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 II

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:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Dutasteride

U.S. FDA Resources

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 ]

Estimated Enrollment:	28
Study Start Date:	March 2007
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A	Drug: Dutasteride 0.5 mg capsule given orally on daily basis Other Name: Avodart
Placebo Comparator: B	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

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

Contacts

Contact: Daniel H. Shevrin, MD

847-570-2515

dshevrin@northshore.org

Locations

United States, Illinois
University of Chicago Hospitals and Clinics	Recruiting
Chicago, Illinois, United States, 60637
Contact: Beth Manchen, RN 773-834-7466 emanchen@medicine.bsd.uchicago.edu
Sub-Investigator: Edward Posadas, MD
Northwestern University Medical Center	Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Brenda Martone, RN 312-695-1366 b-martone@northwestern.edu
Sub-Investigator: Gary MacVicar, MD
NorthShore University HealthSystem	Recruiting
Evanston, Illinois, United States, 60201
Contact: Michelle Britto, RN 847-570-2109 mbritto@northshore.org
Contact: Kelli Shaffer, MS 847-570-4193 kshaffer@northshore.org
Principal Investigator: Daniel H Shevrin, MD

Sponsors and Collaborators

NorthShore University HealthSystem Research Institute

University of Chicago

Northwestern University

Investigators

Principal Investigator:

Daniel H Shevrin, MD

NorthShore University HealthSystem Research Institute

More Information

No publications provided

Responsible Party:	Daniel H. Shevrin, MD/Senior Attending, NorthShore University HealthSystem
ClinicalTrials.gov Identifier:	NCT00668642 History of Changes
Other Study ID Numbers:	EH07-109
Study First Received:	April 28, 2008
Last Updated:	June 24, 2011
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

ClinicalTrials.gov processed this record on February 09, 2012