Soy Isoflavones in Treating Patients Who Are Undergoing Radical Prostatectomy for Stage I or Stage II Adenocarcinoma of the Prostate

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent or delay the development of early cancer. Soy isoflavones may be effective in delaying the development of early prostate cancer. PURPOSE: This randomized phase II trial is studying different regimens of soy isoflavones to compare how well they work in treating patients who are undergoing radical prostatectomy for stage I or stage II prostate cancer (adenocarcinoma).

Detailed Description
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OBJECTIVES: Compare blood/prostate biomarkers of oxidative stress and prostate cancer risk in patients with stage I or II adenocarcinoma of the prostate treated with 3 different dose levels of soy isoflavones before radical prostatectomy. Compare prostatic tissue biomarkers of proliferation and apoptosis in patients treated with these regimens. Determine the potential response, in terms of tumor and prostatic intraepithelial neoplasia grade and volume, extraprostatic extension, and serum prostate-specific antigen level, in patients treated with soy isoflavones and in those treated with placebo. Determine the safety of soy isoflavone supplementation in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, parallel-group study. Patients are stratified according to tumor stage (T1c vs T2). Patients are randomized to 1 of 4 treatment arms. Arm I (control group): Patients receive oral placebo once daily. Arm II: Patients receive oral soy isoflavones and oral placebo once daily. Arm III: Patients receive a higher dose of oral soy isoflavones and oral placebo once daily. Arm IV: Patients receive a higher dose (higher than arm III) of oral soy isoflavones once daily. In all arms, treatment continues for 2-6 weeks (depending on the time from study entry to planned surgery) in the absence of unacceptable toxicity. All patients then undergo radical prostatectomy. Patients are followed at 1 week. PROJECTED ACCRUAL: A total of 100 patients (25 per treatment arm) will be accrued for this study within 12.5 months.

Official Title
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Phase II Clinical Trial of Soy Isoflavones Prior to Radical Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: soy isoflavones
* Procedure: neoadjuvant therapy
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Stage T1c or T2 Disease confined to the prostate gland Planning to undergo radical prostatectomy within the next 3-4 weeks PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic ALT and AST less than 2 times upper limit of normal (ULN) Alkaline phosphatase less than 2 times ULN Renal Not specified Other Fertile patients must use effective barrier contraception Medically cleared for surgery No concurrent thyroid disease PRIOR CONCURRENT THERAPY: Biologic therapy No prior biological therapy for prostate cancer No concurrent biological agents Chemotherapy No prior chemotherapy for prostate cancer No concurrent chemotherapy Endocrine therapy No prior hormonal therapy for prostate cancer No concurrent thyroid hormone replacement medication No concurrent hormonal therapy Radiotherapy Not specified Surgery See Disease Characteristics Other At least 3 months since prior high-dose nutritional supplements No concurrent regular use (more than once weekly) of soy products greater than 50 g of soy protein or 50 mg of soy isoflavone No concurrent high-dose nutritional supplements Standard-dose single multivitamin tablet (e.g., Centrum™) allowed No concurrent herbs No concurrent soy foods No other concurrent isoflavone supplements No other concurrent antineoplastic agents

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo<br>Arm I (control group): Patients receive 4 placebo capsules by mouth daily for three weeks. | Procedure: neoadjuvant therapy<br>* Prostatectomy or Brachytherapy<br>Other: Placebo<br>* Arm I: 4 placebo capsules Arm II: 3 placebo capsules Arm III: 2 placebo capsules<br>|
| Experimental: Soy isoflavones and placebo<br>Arm II: Patients receive oral soy isoflavones (PTI G-2535) 150 mg genistein capsules + 3 placebo capsules by mouth daily for 3 weeks. | Dietary Supplement: soy isoflavones<br> <br> Procedure: neoadjuvant therapy<br>* Prostatectomy or Brachytherapy<br>Other: Placebo<br>* Arm I: 4 placebo capsules Arm II: 3 placebo capsules Arm III: 2 placebo capsules<br>|
| Experimental: Soy Isoflavones/Placebo<br>Arm III: Patients receive oral soy isoflavones (PTI G-2535) 300 mg genistein capsules + 2 placebo capsules by mouth daily for 3 weeks. | Dietary Supplement: soy isoflavones<br> <br> Procedure: neoadjuvant therapy<br>* Prostatectomy or Brachytherapy<br>Other: Placebo<br>* Arm I: 4 placebo capsules Arm II: 3 placebo capsules Arm III: 2 placebo capsules<br>|
| Experimental: Soy Isoflavones<br>Arm IV: Arm III: Patients receive oral soy isoflavones (PTI G-2535) 600 mg genistein capsules by mouth daily for 3 weeks. | Dietary Supplement: soy isoflavones<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative DNA damage as measured by 5-hydroxymethyluridine level |  | at 3 weeks | 
| Lipid oxidation as measured by 8-isoprostane level |  | at 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor size, grade, and extension |  | at 3 weeks | 
| Prostate-specific antigen and prostatic intraepithelial neoplasia grade |  | at 3 weeks | 
| Biomarkers of cell growth, differentiation, and apoptosis |  | at 3 weeks | 
| Toxicity as measured by number and grade of adverse events |  | at 3 weeks | 

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