Selenomethionine and Finasteride Before Surgery or Radiation Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Selenomethionine may slow the growth of prostate cancer. Testosterone can cause the growth of prostate cancer cells. Finasteride may fight prostate cancer by lowering the amount of testosterone the body makes. Giving selenomethionine together with finasteride before surgery or radiation therapy may be an effective treatment for prostate cancer. PURPOSE: This randomized phase II trial is studying how well selenomethionine and finasteride work when given before surgery or radiation therapy in treating patients with stage I or stage II prostate cancer.

Detailed Description
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OBJECTIVES: Primary To investigate the effects of selenomethionine and/or finasteride on key androgen receptor signaling biomarkers (prostate-specific antigen, kallikrein 2, and NKX3.1) in prostate tissue samples from patients with stage I or II prostate cancer. Secondary To analyze the effects of selenomethionine and/or finasteride on apoptosis induction in benign prostate tissue samples from these patients. Tertiary To determine whether responsiveness to selenomethionine and/or finasteride is related to the level of Prx1 in prostate cancer cells. OUTLINE: Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive oral selenomethionine and oral finasteride once daily for 4-5 weeks. Patients then undergo prostatectomy or brachytherapy. Arm II: Patients receive oral placebo and oral finasteride once daily for 4-5 weeks. Patients then undergo prostatectomy or brachytherapy. Arm III: Patients receive oral selenomethionine and oral placebo once daily for 4-5 weeks. Patients then undergo prostatectomy or brachytherapy. Arm IV: Patients receive two oral placebos once daily for 4-5 weeks. Patients then undergo prostatectomy or brachytherapy. Blood samples are collected at baseline and on the day of prostatectomy or brachytherapy. Samples are analyzed for testosterone and 5-α-dihydrotestosterone levels by capillary gas chromatography-mass spectrometry; genetic polymorphisms in the type 2 5-α reductase gene by PCR and sequencing analyses; and selenium levels by atomic absorption spectrophotometry. Additional blood samples will be stored for future analysis of alpha and gamma tocopherol, lycopene, and other vitamin levels. Toenail samples are also collected to provide an indicator of long-term selenium status. Prostate tissue samples are collected during and after prostatectomy or prior to brachytherapy. Samples are analyzed for expression of biomarkers (e.g., prostate-specific antigen, kallikrein 2, and NKX 3.1) by quantitative RT-PCR and apoptosis by TUNEL assay, immunohistochemistry, and ELISA.

Official Title
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A Randomized, Double Blind, Placebo Controlled Clinical Trial of L-SeMet Supplementation and Finasteride Treatment of Patients With Prostate Cancer Prior to Robotic Prostatectomy/Brachytherapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: selenomethionine
* Drug: finasteride
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven adenocarcinoma of the prostate Diagnosed by sextant or greater biopsy Clinical stage < T3 (stage I or II) disease Prostate-specific antigen < 20.0 ng/mL Gleason score < 8 Scheduled to undergo prostatectomy or brachytherapy PATIENT CHARACTERISTICS: Life expectancy > 5 years No other prior malignancy (excluding nonmelanoma skin cancer) in the past 5 years Willing and able to take finasteride, selenomethionine, and/or placebo for 3-5 weeks prior to prostatectomy/brachytherapy PRIOR CONCURRENT THERAPY: More than 1 year since prior finasteride, dutasteride, Sereona repens (saw palmetto), or any other 5-α reductase inhibitor No prior hormonal therapy or radiotherapy More than 30 days since prior and no concurrent participation in any other clinical trial involving a medical, surgical, nutritional, or life-style intervention (e.g., dietary modification or exercise) No concurrent selenium dietary supplement at doses > 200 mg/day, including multivitamin supplements At least 30 days since > 200mg/day of prior selenium dietary supplement No other concurrent hormonal therapy, including 5-α reductase inhibitors (e.g., finasteride or dutasteride); anti-androgens (e.g., bicalutamide, flutamide, or ketoconazole); or luteinizing hormone-releasing hormone agonists (e.g., leuprolide acetate, goserelin acetate, or abarelix)

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral selenomethionine and oral finasteride once daily for 4-5 weeks. | Dietary Supplement: selenomethionine<br>* Given orally<br>Drug: finasteride<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive oral placebo and oral finasteride once daily for 4-5 weeks. | Drug: finasteride<br>* Given orally<br>Other: placebo<br>* Given orally<br>|
| Experimental: Arm III<br>Patients receive oral selenomethionine and oral placebo once daily for 4-5 weeks. | Dietary Supplement: selenomethionine<br>* Given orally<br>Other: placebo<br>* Given orally<br>|
| Placebo Comparator: Arm IV<br>Patients receive two oral placebos once daily for 4-5 weeks. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Selenium and Finasteride and Their Combination on PSA Level | Compare PSA levels with Finasteride Placebo + Selenium Placebo group (Arm C). The Wilcoxon Rank Sum Test was used to test the difference of PSA levels of Arm A, Arm B, Arm D with Arm C. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction | Compare cleaved caspase 3 values with Finasteride Placebo + Selenium Placebo group (Arm C). The Wilcoxon Rank Sum Test was used to test the difference of cleaved caspase 3 values of Arm A, Arm B, Arm D with Arm C. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer