S9917, Selenium in Preventing Cancer in Patients With Neoplasia 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 the development of cancer. The use of selenium may be an effective way to prevent prostate cancer in patients who have neoplasia of the prostate. PURPOSE: Randomized phase III trial to study the effectiveness of selenium in preventing prostate cancer in patients who have neoplasia of the prostate.

Detailed Description
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OBJECTIVES: Compare the effects of selenium versus placebo on the 3-year incidence rate of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia. Compare the toxicity of these regimens in these patients. Compare the effects of these regimens on the rate of increase in prostate-specific antigen (PSA) in these patients. Compare the effects of these regimens on prostatic cellular proliferation and apoptosis, degradation of basal cell integrity of prostatic ducts, and changes in nuclear chromatin patterns in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (40-60 vs 61 and over), race (African American vs other), baseline PSA (less than 4 ng/mL vs 4-10 ng/mL), concurrent vitamin E supplementation (yes vs no), and cores obtained from initial biopsy (10 or more vs less than 10). Patients are randomized to 1 of 2 arms. Arm I: Patients receive oral selenium once daily. Arm II: Patients receive oral placebo once daily. Treatment in both arms continues for 3 years in the absence of progression to prostate cancer or unacceptable toxicity. Patients are followed every 6 months for 2 years and then annually for 8 years. PROJECTED ACCRUAL: A total of 465 patients will be randomized for this study.

Official Title
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L-Selenium-Based Chemoprevention Of Prostate Cancer Among Men With High Grade Prostatic Intraepithelial Neoplasia

Conditions
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Precancerous/Nonmalignant Condition, Prostate Cancer

Intervention / Treatment
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* Drug: L-selenomethionine
* Drug: L-selenomethionine placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of high-grade prostatic intraepithelial neoplasia with no evidence of cancer Documented by a digital rectal exam and biopsy of the prostate with transrectal ultrasound guidance (required if fewer than 6 cores obtained in biopsy) meeting one of the following conditions: Biopsy yielded fewer than 10 cores within the past 24 months OR yielded more than 10 cores 6-24 months before study Biopsy yielded 10 or more cores within the past 6 months PSA ≤ 10 ng/mL (≤ 5 ng/mL for patients who have received finasteride or other androgen suppressor within the past 2 months) American Urological Association symptom score of less than 20 PATIENT CHARACTERISTICS: Age: 40 and over Performance status: SWOG 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer that is in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy See Disease Characteristics No concurrent finasteride or any other androgen suppressor Radiotherapy Not specified Surgery Not specified Other At least 30 days since prior daily dietary supplements containing 50 micrograms or more of selenium No concurrent daily dietary supplements containing more than 50 micrograms of selenium

Ages Eligible for Study
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Minimum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: L-selenomethionine<br>L-selenomethionine (Selenium)one tablet by mouth daily for 3 years. | Drug: L-selenomethionine<br>* Randomization between active L-selenomethionine and placebo<br>* Other names: Selenium;|
| Placebo Comparator: L-selenomethionine placebo<br>L-selenomethionine placebo one tablet by mouth daily for 3 years | Drug: L-selenomethionine placebo<br>* Randomization between active L-selenomethionine and placebo<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Carcinoma of the Prostate as Measured by Biopsy | The primary endpoint is biopsy-proven presence/absence of carcinoma of the prostate within 3 years after randomization to treatment. An end-of-study biopsy at 3 years after randomization will be used to determine presence/absence of prostate carcinoma in those patients not previously diagnosed with prostate carcinoma on study. Biopsies performed within ± 90 days of the 3-year anniversary will be considered end-of-study biopsies. Pathologically confirmed presence of prostate carcinoma may be determined at any time during the 3 years and 90 days after randomization, but absence can only be determined by the end-of-study biopsy. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | 3 months after randomization and then every 3 months for 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, high grade prostatic intraepithelial neoplasia