Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer
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.
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.
Interventions
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Selenium and Finasteride and Their Combination on PSA Level | 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
| Measure | Time frame | Description |
|---|---|---|
| Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Finasteride + Selenium Placebo Patients receive oral placebo and oral finasteride once daily for 4-5 weeks.
Finasteride: Given orally
Placebo: Given orally | 13 |
| Arm B: Finasteride + Selenium Patients receive oral selenomethionine and oral finasteride once daily for 4-5 weeks.
Selenomethionine: Given orally
Finasteride: Given orally | 15 |
| Arm C: Finasteride Placebo + Selenium Placebo Patients receive two oral placebos once daily for 4-5 weeks.
Placebo: Given orally | 14 |
| Arm D: Finasteride Placebo + Selenium Patients receive oral selenomethionine and oral placebo once daily for 4-5 weeks.
Selenomethionine: Given orally
Placebo: Given orally | 13 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm B: Finasteride + Selenium | Arm C: Finasteride Placebo + Selenium Placebo | Arm D: Finasteride Placebo + Selenium | Total | Arm A: Finasteride + Selenium Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 7.7 | 61.2 years STANDARD_DEVIATION 5.2 | 61.9 years STANDARD_DEVIATION 6.8 | 60.8 years STANDARD_DEVIATION 6.9 | 57.9 years STANDARD_DEVIATION 7.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 0 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 13 Participants | 13 Participants | 50 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 13 Participants | 55 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 3 / 15 | 4 / 14 | 3 / 13 |
| serious Total, serious adverse events | 0 / 13 | 2 / 15 | 1 / 14 | 2 / 13 |
Outcome results
Primary
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.
Time frame: 1 year
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Finasteride + Selenium Placebo | Effects of Selenium and Finasteride and Their Combination on PSA Level | 1.9 ng/mL |
| Arm B: Finasteride + Selenium | Effects of Selenium and Finasteride and Their Combination on PSA Level | 1.9 ng/mL |
| Arm C: Finasteride Placebo + Selenium Placebo | Effects of Selenium and Finasteride and Their Combination on PSA Level | 2.0 ng/mL |
| Arm D: Finasteride Placebo + Selenium | Effects of Selenium and Finasteride and Their Combination on PSA Level | 2.1 ng/mL |
p-value: 0.5137Wilcoxon (Mann-Whitney)
p-value: 0.8994Wilcoxon (Mann-Whitney)
p-value: 0.3463Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: 1 year
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Finasteride + Selenium Placebo | Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction | 0.1 percentage of apoptotic cells |
| Arm B: Finasteride + Selenium | Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction | 0 percentage of apoptotic cells |
| Arm C: Finasteride Placebo + Selenium Placebo | Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction | 0 percentage of apoptotic cells |
| Arm D: Finasteride Placebo + Selenium | Effects of Selenium and Finasteride and Their Combination on Apoptosis Induction | 0 percentage of apoptotic cells |
p-value: 0.2609Wilcoxon (Mann-Whitney)
p-value: 0.7504Wilcoxon (Mann-Whitney)
p-value: 0.9727Wilcoxon (Mann-Whitney)