Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Dutasteride and Androgen-Ablation Therapy in Treating Patients With Localized Prostate Cancer Who Have Undergone Radiation Therapy and/or Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	45 to 80	NCI	UWCC-6408 6408, UWCC-UW 6408, UWCC- 06-4211-H/B, NCT00516815

Objectives

Primary

1. To assess the effect of dutasteride on the length of the off-treatment interval in patients receiving intermittent androgen-ablation therapy for localized prostate cancer.

Secondary

1. To assess the effect of dutasteride on the PSA nadir after 9 months of androgen-deprivation therapy.
2. To assess the effect of dutasteride on serum testosterone and dihydrotestosterone levels.
3. To assess the effect of dutasteride on the time to onset of androgen-independent prostate cancer (i.e., rising PSA with testosterone < 50 ng/mL).
4. To assess the safety and tolerability of dutasteride when administered in combination with intermittent androgen-ablation therapy.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate
  • Localized disease
  • Known Gleason grade
• Received prior external-beam radiotherapy, brachytherapy, or radical prostatectomy
• Candidate for intermittent androgen-ablation therapy
• Minimum of 3 PSA values above the nadir PSA measured ≥ 1 month apart after treatment AND meets 1 of the following criteria:
  • PSA level ≥ 2.0 ng/mL and < 100 ng/mL in patients who underwent prior radical prostatectomy with or without radiotherapy
  • PSA level ≥ 3.0 ng/mL and < 100 ng/mL in patients who underwent external beam radiotherapy (at any time) or brachytherapy > 3 years ago
  • PSA level ≥ 6.0 ng/mL and < 100 ng/mL in patients who underwent brachytherapy within the past 3 years
• Serum testosterone ≥ 250 ng/dL
• Negative bone scan within the past 12 months
• No distant metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior treatment for prostate cancer with any of the following:
  • Chemotherapy
  • Hormonal therapy (e.g., megestrol, medroxyprogesterone, cyproterone, or diethylstilbestrol) within the past year
    • May have received ≤ 12 months of neoadjuvant or adjuvant androgen-deprivation therapy provided the therapy was discontinued > 1 year ago
  • Glucocorticoids (except inhaled or topical drugs) within the past 3 months
  • Ketoconazole
  • Luteinizing hormone releasing-hormone analogs (e.g., leuprolide or goserelin) or nonsteroidal antiandrogens (e.g., bicalutamide or flutamide) within the past year
• More than 30 days since prior and no other concurrent investigational agents
• More than 1 year since prior and no concurrent use of the following medications:
  • Finasteride
  • Dutasteride
  • Other investigational 5α-reductase inhibitors
  • Anabolic steroids
  • Medications with antiandrogenic properties (e.g. spironolactone, flutamide, ketoconazole, metronidazole, progestational agents)
  • Over-the-counter or herbal preparations such as cimetidine, saw palmetto, selenium (> 75 mcg), or vitamin E (> 100 IU)
    • Concurrent use of a multivitamin is allowed provided the amounts of vitamin E and selenium do not exceed 100 IU and 75 mcg, respectively
    • Patients who had been using saw palmetto are eligible provided a 2 week washout period is observed
    • Patients who had been using vitamin E > 100 IU but ≤ 400 IU are eligible provided a 2 week washout period is observed
• No coronary bypass surgery within the past 6 months

Patient Characteristics:

Inclusion criteria:

• ECOG performance status 0-1
• Able to read and write, understand instructions related to study procedures, and give written informed consent
• Able to swallow and retain oral medication
• Able and willing to participate in the full study

Exclusion criteria:

• Unstable serious concurrent medical conditions including, but not limited to, any of the following:
  • Myocardial infarction
  • Unstable angina
  • Cardiac arrhythmias
  • Clinically evident congestive heart failure or cerebrovascular accident within the past 6 months
  • Uncontrolled diabetes
  • Peptic ulcer disease
• Alkaline phosphatase, ALT, or AST > 2 times upper limit of normal (ULN)
• Bilirubin > 1.5 times ULN
• Serum creatinine > 1.5 times ULN
• Other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or Ta bladder cancer with negative surveillance cystoscopy within the past 2 years
• History or current evidence of drug or alcohol abuse within the past year
• History of any illness that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the patient
• Known hypersensitivity to any 5α-reductase inhibitor or to any drug chemically related to dutasteride
• Known hypersensitivity to bicalutamide or to any drug chemically related to bicalutamide

Expected Enrollment

Outcomes

Time to PSA > 5.0 ng/mL during the off-treatment interval during intermittent androgen-ablation therapy

Time to androgen-independent prostate cancer, as defined by a rising PSA with testosterone < 50 ng/mL
Adverse events as assessed by NCI CTCAE v3.0
Clinical laboratory evaluations (i.e., hematology, biochemistry, and total PSA)
Levels of serum testosterone and dihydrotestosterone (DHT)
Quality of life as measured by the FACT-P, IPSS, and the PAS SFI at baseline and at 9 and 24 months
PSA nadir at the end of 9 months of androgen-ablation therapy
Serum testosterone and DHT levels achieved during intermittent androgen-ablation therapy

Outline

This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. All patients receive intermittent androgen-ablation therapy (IAAT) comprising oral bicalutamide once daily, beginning concurrently with study medication, for 9 months and a depot injection of luteinizing hormone-releasing hormone analog once every 3 months for 9 months beginning at 3 months after initiation of study medication. An off-treatment interval (i.e., off IAAT) follows after completion of 9 months of IAAT.

• Arm I: Patients receive oral dutasteride once daily for up to 9 months* in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive oral placebo once daily for up to 9 months* in the absence of disease progression or unacceptable toxicity.

 [Note: *Patients with a serum PSA value < 1.0 ng/mL at the end of 9 months continue dutasteride once daily for up to 21 months until serum PSA increases to ≥ 5.0 ng/mL.]

Patients undergo blood sample collection at baseline and periodically for pharmacodynamic analysis. Samples are analyzed for circulating levels of serum testosterone and dihydrotestosterone.

Quality of life is assessed at baseline and 9 or 24 months.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Celestia Higano, MD, Principal investigator		Ph: 206-288-1152

U.S.A.
Washington
	Kirkland
	Cascade Cancer Center at Evergreen Hospital Medical Center
		Brenda Havens	Ph:  425-899-3181
			Email: bhavens@cascadecancercenter.com
	Mount Vernon
	Skagit Valley Hospital Cancer Care Center
		Robert Raish, MD	Ph:  360-428-2146
	Seattle
	Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center
		Jacqueline Vuky, MD	Ph:  206-223-6193
			Email: jacqueline.vuky@vmmc.org
	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
		Alma MacAraeg	Ph:  206-288-1349
			Email: almam@u.washington.edu
	University Cancer Center at University of Washington Medical Center
		Alma MacAraeg	Ph:  206-288-1349
			Email: almam@u.washington.edu
	Tacoma
	MultiCare Regional Cancer Center at Tacoma General Hospital
		Richard Shine, PharmD	Ph:  253-403-7250
			Email: Richard.Shine@multicare.org

Registry Information
Official Title		Multicentre, Double-Blind Study Comparing 0.5mg Dutasteride vs. Placebo Daily in Men Receiving Intermittent Androgen Ablation Therapy for Prostate Cancer
Trial Start Date		2006-12-13
Trial Completion Date		2009-12-13 (estimated)
Registered in ClinicalTrials.gov		NCT00516815
Date Submitted to PDQ		2007-07-26
Information Last Verified		2009-08-24
NCI Grant/Contract Number		CA15704

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