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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Other: placebo; Dietary supplement: selenomethionine; Drug: finasteride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: James L. Mohler, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: August 15, 2008
• First Submitted That Met QC Criteria: August 15, 2008
• First Posted (Estimated): August 18, 2008

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Trace Elements; Micronutrients; Hormone Antagonists; Steroid Synthesis Inhibitors; Antioxidants; 5-alpha Reductase Inhibitors; Selenium; Finasteride
• Other Study ID Numbers: CDR0000611962; RPCI I 104607 (Other Identifier: Roswell Park Cancer Institute)