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:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment
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 2012
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

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

d-shevrin@northwestern.edu

Locations

United States, Illinois
Evanston Northwestern Healthcare	Recruiting
Evanston, Illinois, United States, 60201
Contact: Michelle Britto, RN 847-570-2109 mbritto@enh.org
Contact: Joanna Hill, RN 847-570-1768 jhill@enh.org
Principal Investigator: Daniel H Shevrin, MD
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

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:	Evanston Northwestern Healthcare ( Daniel H. Shevrin, MD/Senior Attending )
Study ID Numbers:	EH07-109
Study First Received:	April 28, 2008
Last Updated:	April 28, 2008
ClinicalTrials.gov Identifier:	NCT00668642 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Genital Neoplasms, Male
Prostatic Diseases
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors
Urogenital Neoplasms
Genital Diseases, Male

Hormones
Pharmacologic Actions
Dutasteride
Neoplasms
Neoplasms by Site
Prostatic Neoplasms
Androgens

ClinicalTrials.gov processed this record on February 08, 2010