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

• ClinicalTrials.gov Identifier: NCT00736645
• Recruitment Status: Completed
• First Posted: August 18, 2008
• Results First Posted: November 28, 2017
• Last Update Posted: November 28, 2017
• Sponsor: Roswell Park Cancer Institute
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Dietary Supplement: selenomethionine; Drug: finasteride; Other: placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: August 2008
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

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.	Drug: finasteride; Given orally; Other: placebo; Given orally
Experimental: Arm III; Patients receive oral selenomethionine and oral placebo once daily for 4-5 weeks.	Dietary Supplement: selenomethionine; Given orally; Other: placebo; Given orally
Placebo Comparator: Arm IV; Patients receive two oral placebos once daily for 4-5 weeks.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures :

1. Effects of Selenium and Finasteride and Their Combination on PSA Level [ Time Frame: 1 year ]
   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.

Secondary Outcome Measures :

1. Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction [ Time Frame: 1 year ]
   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263-0001

Sponsors and Collaborators

Roswell Park Cancer Institute

Investigators

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

More Information

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00736645
• Other Study ID Numbers: CDR0000611962; RPCI I 104607 ( Other Identifier: Roswell Park Cancer Institute )
• First Posted: August 18, 2008
• Results First Posted: November 28, 2017
• Last Update Posted: November 28, 2017
• Last Verified: October 2017

Keywords provided by Roswell Park Cancer Institute:

adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Selenium; Finasteride; 5-alpha Reductase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Urological Agents; Antioxidants; Protective Agents; Trace Elements; Micronutrients