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

Study Overview
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Brief Summary
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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).

Detailed Description
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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. Prostate-specific antigen (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.

Official Title
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Effect of Dutasteride on Androgen-Response Gene Expression During the Tumor Regrowth Phase of Intermittent Androgen Ablation Therapy in Patients With Advanced Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Dutasteride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven prostate cancer Patients are hormone-naive Patients either to begin androgen ablation therapy with luteinizing hormone-releasing hormone (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) Eastern Cooperative Oncology Group (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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Dutasteride During First Off-Cycle<br>Arm A patients received dutasteride (0.5 mg/day) during the first off-cycle and received placebo during the second off-cycle | Drug: Dutasteride<br>* 0.5 mg capsule given orally on daily basis<br>* Other names: Avodart;|
| Placebo Comparator: B: Placebo During First Off-Cycle<br>Arm B patients received placebo during the first off-cycle and received dutasteride (0.5 mg/day) during the second off-cycle | Drug: Placebo<br>* Identical placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Expression of U19 Gene in Tumor From Prostate Gland During First Off-cycle. | Calculation of the level of gene expression of the U19 tumor suppressor gene compared between the 2 arms at the end of off-treatment cycle 1. | At the end of off-cycle 1 defined by when the testosterone level reaches normal (approximately 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of Prostate-specific Antigen (PSA) Doubling Time During First Off-cycle | Calculation of number of months when baseline PSA doubles compared between the 2 arms at the end of off-treatment cycle 1. | At month 9 and ongoing monthly until end of off-cycle 1 defined by when the testosterone level reaches normal (approximately 6 months) |