SELECT: S0000 Selenium and Vitamin E in Preventing Prostate Cancer

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00006392
• Collaborator: National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other), Cancer and Leukemia Group B (Other), NCIC Clinical Trials Group (Other)
• Enrollment: 35,533
• Locations: 13
• Arms: 4
• Duration (Months): 134
• Patients Per Site: 2733.3
• Patients Per Site Per Month: 20.4

Study Details

Study Description

Brief Summary

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known which regimen of selenium and/or vitamin E may be more effective in preventing prostate cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of selenium and vitamin E, either alone or together, in preventing prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Vitamin E; Drug: Selenium; Other: Vitamin E placebo; Other: selenium placebo	Phase 3

Detailed Description

OBJECTIVES:

• Compare the effect of selenium and vitamin E administered alone vs in combination on the clinical incidence of prostate cancer.

• Compare the effect of these prevention regimens on the incidence of lung cancer, colorectal cancer, and all cancers combined in participants on this study.

• Compare the effect of these prevention regimens on prostate cancer-free survival, lung cancer-free survival, colorectal cancer-free survival, cancer-free survival, overall survival, and serious cardiovascular events in these participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35533 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Selenium and Vitamin E Cancer Prevention Trial (SELECT) for Prostate Cancer
• Study Start Date: Jul 1, 2001
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin E + selenium placebo vitamin E and selenium placebo daily for 7-12 years	Drug: Vitamin E; 400 IU daily by mouth for 7-12 years; Other Names: alpha tocopherol ; Other: selenium placebo; daily for 7-12 years; Other Names: placebo
Experimental: Selenium + vitamin E placebo selenium and vitamin E placebo daily for 7-12 years	Drug: Selenium; 200 mcg daily for 7-12 years; Other Names: L-selenomethionine ; Other: Vitamin E placebo; daily for 7-12 years; Other Names: placebo
Experimental: Vitamin E + selenium vitamin E and selenium placebo daily for 7-12 years	Drug: Vitamin E; 400 IU daily by mouth for 7-12 years; Other Names: alpha tocopherol ; Drug: Selenium; 200 mcg daily for 7-12 years; Other Names: L-selenomethionine
Placebo Comparator: Vitamin E placebo + selenium placebo vitamine E placebo and selenium placebo daily for 7-12 years	Other: Vitamin E placebo; daily for 7-12 years; Other Names: placebo ; Other: selenium placebo; daily for 7-12 years; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Prostate Cancer [Every six months for 7 to 12 years depending on when the participant was randomized.]

   Participants are seen at the study site every six month for an update of medical events. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation.

Secondary Outcome Measures

1. Number of Participants With Lung Cancer [Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.]

   Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.

2. Number of Participants With Colorectal Cancer [Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.]

   Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.

3. Number of Participants With Any Diagnosis of Cancer [Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.]

   Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.

4. Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival [Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.]

   Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation. Other cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized.

5. Number of Participants With Serious Cardiovascular Events [Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.]

   Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Cardiovascular events are based on self-report and are not confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 120 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

DISEASE CHARACTERISTICS:

• Healthy male volunteers

• Digital rectal examination (DRE) deemed not suspicious for prostate cancer performed within 364 days prior to study entry

• Participants with a suspicious DRE are ineligible even if a recent or subsequent biopsy is negative for cancer

• Total prostate-specific antigen ≤ 4.0 ng/mL within 364 days prior to study entry

• No prior prostate cancer or high-grade (grade 2-3) prostatic intraepithelial neoplasia

PATIENT CHARACTERISTICS:

Age:

• See Disease Characteristics

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• Systolic blood pressure < 160 mm Hg

• Diastolic blood pressure < 90 mm Hg

• No history of hemorrhagic stroke

Other:

• No malignancies within the past 5 years except basal cell or squamous cell skin cancer

• No uncontrolled medical illness

• No retinitis pigmentosa

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 7 years since prior randomization to SWOG-9217, with completion of end-of-study biopsy requirement

• No additional concurrent selenium or vitamin E (contained in individual supplements, antioxidant mix, or multivitamin)

• Concurrent multivitamins allowed (supplied on study)

• No concurrent anticoagulation therapy (e.g., warfarin)

• Concurrent prophylactic aspirin (average daily dose no greater than 175 mg/day) allowed

• Concurrent daily aspirin dose ≤ 81 mg for participants receiving clopidogrel

• Concurrent anti-hypertension medication allowed

• No concurrent participation in another study involving a medical, surgical, nutritional, or life-style intervention (unless no longer receiving the intervention and are in the follow-up phase only)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
2	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
3	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
4	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
5	St. John's Regional Health Center	Springfield	Missouri	United States	65804
6	Good Samaritan Hospital Cancer Treatment Center	Cincinnati	Ohio	United States	45220
7	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
8	Tod Children's Hospital	Youngstown	Ohio	United States	44501
9	LaFortune Cancer Center at St. John Medical Center	Tulsa	Oklahoma	United States	74104
10	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-0001
11	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
12	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
13	U.T. Cancer Institute at University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920-6999

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• Eastern Cooperative Oncology Group
• Cancer and Leukemia Group B
• NCIC Clinical Trials Group

Investigators

• Study Chair: Eric Klein, MD, The Cleveland Clinic
• Study Chair: Philip J. Walther, MD, PhD, Duke University
• Study Chair: Laurence H. Klotz, MD, Toronto Sunnybrook Regional Cancer Centre
• Study Chair: Scott M. Lippman, M.D., MD Anderson
• Study Chair: Ian M. Thompson, M.D., University of Texas
• Study Chair: J. Michael Gaziano, M.D., MAVERIC
• Study Chair: Daniel D Karp, M.D., Beth Israel Deaconess
• Study Chair: Fadlo R. Khuri, M.D., MD Anderson
• Study Chair: Michael M Lieber, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cook ED, Moody-Thomas S, Anderson KB, Campbell R, Hamilton SJ, Harrington JM, Lippman SM, Minasian LM, Paskett ED, Craine S, Arnold KB, Probstfield JL. Minority recruitment to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Clin Trials. 2005;2(5):436-42.
• El-Bayoumy K. The negative results of the SELECT study do not necessarily discredit the selenium-cancer prevention hypothesis. Nutr Cancer. 2009;61(3):285-6. doi: 10.1080/01635580902892829.
• Hoque A, Albanes D, Lippman SM, Spitz MR, Taylor PR, Klein EA, Thompson IM, Goodman P, Stanford JL, Crowley JJ, Coltman CA, Santella RM. Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cancer Causes Control. 2001 Sep;12(7):627-33.
• Kristal AR, King IB, Albanes D, Pollak MN, Stanzyk FZ, Santella RM, Hoque A. Centralized blood processing for the selenium and vitamin E cancer prevention trial: effects of delayed processing on carotenoids, tocopherols, insulin-like growth factor-I, insulin-like growth factor binding protein 3, steroid hormones, and lymphocyte viability. Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):727-30.
• Lippman SM, Goodman PJ, Klein EA, Parnes HL, Thompson IM Jr, Kristal AR, Santella RM, Probstfield JL, Moinpour CM, Albanes D, Taylor PR, Minasian LM, Hoque A, Thomas SM, Crowley JJ, Gaziano JM, Stanford JL, Cook ED, Fleshner NE, Lieber MM, Walther PJ, Khuri FR, Karp DD, Schwartz GG, Ford LG, Coltman CA Jr. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst. 2005 Jan 19;97(2):94-102.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00006392
• Other Study ID Numbers: CDR0000068277; S0000; U10CA037429; NCT00076128
• First Posted: Jan 27, 2003
• Last Update Posted: Nov 20, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by Southwest Oncology Group: prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Vitamins; Vitamin E; Tocopherols; Tocotrienols; alpha-Tocopherol; Selenium

Study Results

Participant Flow

Recruitment Details	Men were randomized at 427 study sites in the US, Puerto Rico and Canada between August 22, 2001 and June 24, 2004.
Pre-assignment Detail	Prior to randomization, there was a three month formal pre-randomization period with no placebo run-in capsules to give potential participants to decide if they would agree to stop disallowed over-the-counter supplements of selenium or vitamin E. By returning for randomization, they exhibited their willingness to adhere to the trial.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Period Title: Overall Study
STARTED	8904	8910	8863	8856
COMPLETED	8737	8752	8703	8696
NOT COMPLETED	167	158	160	160

Baseline Characteristics

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo	Total
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium	Total of all reporting groups
Overall Participants	8737	8752	8703	8696	34888
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	62.4	62.6	62.3	62.6	62.3
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	8737 100%	8752 100%	8703 100%	8696 100%	34888 100%
Race/Ethnicity, Customized (Participant) [Number]
White	6890	6942	6874	6863	27569
African American	1107	1053	1076	1078	4314
Hispanic (non-African American)	477	481	484	492	1934
Hispanic (African American)	103	86	95	76	360
Other	160	190	174	187	711
Region of Enrollment (participants) [Number]
United States	7463 85.4%	7471 85.4%	7427 85.3%	7428 85.4%	29789 85.4%
Canada	909 10.4%	915 10.5%	911 10.5%	904 10.4%	3639 10.4%
Puerto Rico	365 4.2%	366 4.2%	365 4.2%	364 4.2%	1460 4.2%
Age (categorical) (participants) [Number]
50 - 54 years	402 4.6%	337 3.9%	385 4.4%	355 4.1%	1479 4.2%
55 - 64 years	5143 58.9%	5076 58%	5052 58%	5078 58.4%	20349 58.3%
65 - 74 years	2641 30.2%	2733 31.2%	2731 31.4%	2702 31.1%	10807 31%
>= 75 years	551 6.3%	606 6.9%	535 6.1%	561 6.5%	2253 6.5%
Education (highest) (Participant) [Number]
<= High school graduate or GED	1875	1917	1898	1993	7683
Some college/vocational school	2387	2327	2348	2291	9353
>= College graduate	4394	4430	4372	4317	17513
Unknown/missing	81	78	85	95	339
PSA (ng/ml) (Participant) [Number]
0.1 - 1.0	4208	4218	4213	4122	16761
1.1 - 2.0	2653	2661	2666	2728	10708
2.1 - 3.0	1228	1211	1149	1168	4756
3.1 - 4.0	634	652	659	666	2611
> 4.0	3	2	1	5	11
Unknown/missing	11	8	15	7	41
Smoking status (Participant) [Number]
Never	3752	3780	3666	3682	14880
Current	659	631	670	655	2615
Former	4194	4214	4242	4208	16858
Ever (unknown status)	55	61	56	63	235
Unknown	77	66	69	88	300

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Prostate Cancer
Description	Participants are seen at the study site every six month for an update of medical events. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation.
Time Frame	Every six months for 7 to 12 years depending on when the participant was randomized.

Outcome Measure Data

Analysis Population Description

All randomized eligible men not at 2 sites for which the DSMC said the data could not be used due to participant and data management issues as well as regulatory problems.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Measure Participants	8737	8752	8703	8696
Number [participants]	473 5.4%	432 4.9%	437 5%	416 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments	Per study design, with a sample size of 32,400 men, using a 1-sided alpha=.005 level (equivalent to a 2-sided alpha=.01 level) there was 96% power to detect a 25% reduction in prostate cancer for either agent vs. Placebo.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< .01
	Comments	The p-value was adjusted for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 99%; 0.95 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selenium, Placebo
	Comments	Per study design, with a sample size of 32,400 men, using a 1-sided alpha=.005 level (equivalent to a 2-sided alpha=.01 level) there was 96% power to detect a 25% reduction in prostate cancer for either agent vs. Placebo.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< .01
	Comments	The p-value was adjusted for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 99%; 0.87 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Placebo
	Comments	Per study design, with a sample size of 32,400 men, using a 1-sided alpha=.005 level (equivalent to a 2-sided alpha=.01 level) there was 99% power to detect a 44% reduction in prostate cancer for combination vs. Placebo.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< .01
	Comments	The p-value was adjusted for multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	() 99%; .88 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Lung Cancer
Description	Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time Frame	Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.

Outcome Measure Data

Analysis Population Description

All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Measure Participants	8737	8752	8703	8696
Number [participants]	67 0.8%	75 0.9%	78 0.9%	67 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	The trial was designed to study prostate cancer and lung cancer has a lower incidence rate, there was limited power to look at lung cancer incidence. A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0
	Confidence Interval	() 99%; .64 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selenium, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .01
	Comments	The trial was designed to study prostate cancer and lung cancer has a lower incidence rate, there was limited power to look at lung cancer incidence. A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 99%; 0.73 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>.01
	Comments	The trial was designed to study prostate cancer and lung cancer has a lower incidence rate, there was limited power to look at lung cancer incidence. A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 99%; 0.90 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

3. Secondary Outcome

Title	Number of Participants With Colorectal Cancer
Description	Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time Frame	Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.

Outcome Measure Data

Analysis Population Description

All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Measure Participants	8737	8752	8703	8696
Number [participants]	66 0.8%	63 0.7%	77 0.9%	60 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments	The trial was designed to study prostate cancer and colorectal cancer has a lower incidence rate, there was limited power to look at colorectal cancer incidence.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 99%; 0.69 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selenium, Placebo
	Comments	The trial was designed to study prostate cancer and colorectal cancer has a lower incidence rate, there was limited power to look at colorectal cancer incidence.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 99%; 0.66 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Placebo
	Comments	The trial was designed to study prostate cancer and colorectal cancer has a lower incidence rate, there was limited power to look at colorectal cancer incidence.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 99%; 0.82 to 2.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

4. Secondary Outcome

Title	Number of Participants With Any Diagnosis of Cancer
Description	Participants are seen at the study site every six month for an update of medical events. Cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time Frame	Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.

Outcome Measure Data

Analysis Population Description

All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Measure Participants	8737	8752	8703	8696
Number [participants]	856 9.8%	837 9.6%	846 9.7%	824 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments	The power to look at all cancer incidence is greater than 90%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 99%; 0.91 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selenium, Placebo
	Comments	The power to look at all cancer incidence is greater than 90%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 99%; 0.89 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Placebo
	Comments	The power to look at all cancer incidence is greater than 90%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	() 99%; 0.90 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

5. Secondary Outcome

Title	Prostate Cancer Free Survival; Lung Cancer-free Survival, Colorectal Cancer-free Survival, Cancer-free Survival, Overall Survival
Description	Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Prostate cancer diagnosis is based on participant report followed by the submission of a pathologic sample to central pathology review for confirmation. Other cancer diagnoses are based on participant report. Medical records for non-prostate cancers were collected but they were not pathologically confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time Frame	Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.

Outcome Measure Data

Analysis Population Description

All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues. Deaths include those reported as SAEs as well as non-SAE deaths as this was a prevention trial with older generally healthy men at baseline who were followed for a long time.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Measure Participants	8737	8752	8703	8696
All deaths	358 4.1%	378 4.3%	359 4.1%	382 4.4%
All cancer deaths	106 1.2%	128 1.5%	117 1.3%	125 1.4%
Prostate cancer deaths	0 0%	1 0%	0 0%	0 0%
Lung cancer deaths	38 0.4%	45 0.5%	39 0.4%	41 0.5%
Colorectal cancer deaths	13 0.1%	10 0.1%	15 0.2%	10 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments	Only results from overall survival are presented as the number of cancer-specific deaths is too few to be meaningful.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	() 99%; 0.77 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo is the denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selenium, Placebo
	Comments	Only results from overall survival are presented as the number of cancer-specific deaths is too few to be meaningful.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 99%; 0.82 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Placebo
	Comments	Only results from overall survival are presented as the number of cancer-specific deaths is too few to be meaningful.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 99%; 0.77 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Number of Participants With Serious Cardiovascular Events
Description	Participants are seen at the study site every six month for an update of medical events. If the participant has been diagnosed with prostate cancer, study site visits are once a year. Cardiovascular events are based on self-report and are not confirmed. Follow-up was planned for seven to 12 years depending on when the participant was randomized.
Time Frame	Participants are assessed for medical every six months for 7 to 12 years depending on when he was randomized . Upon diagnosis of prostate cancer, updates are annual.

Outcome Measure Data

Analysis Population Description

All randomized eligible participants excluding all men from 2 study sites that the DSMC said to exclude due to poor participant/data management and regulatory issues.

Arm/Group Title	Vitamin E	Selenium	Combination	Placebo
Arm/Group Description	Vitamin E + matching placebo for selenium	Selenium + matching placebo for vitamin E	Vitamin E + selenium	Matching placebo for vitamin E + matching placebo for selenium
Measure Participants	8737	8752	8703	8696
Number [participants]	1034 11.8%	1080 12.3%	1041 12%	1050 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin E, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 99%; 0.88 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Selenium, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 99%; 0.92 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Combination, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	> .05
	Comments	A 99% CI (rather than a 95% CI) was used to adjust for the multiple comparisons.
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 99%; 0.89 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	The placebo was the denominator.

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Study site visits, collected by CRA based on participant interview and annual limited physical exam
Arm/Group Title	Selenium Alone		Combination		Placebo		Vitamin E Alone
Arm/Group Description	Selenium + placebo for vitamin E		Selenium + vitamin E		Placebo for selenium + placebo for vitamin E		Vitamin E + placebo for selenium
All Cause Mortality
	Selenium Alone		Combination		Placebo		Vitamin E Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Selenium Alone		Combination		Placebo		Vitamin E Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/8752 (1.1%)		93/8702 (1.1%)		108/8696 (1.2%)		99/8737 (1.1%)
Cardiac disorders
Arrhythmia, NOS	3/8752 (0%)		2/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Cardiac ischemia/infarction	25/8752 (0.3%)		26/8702 (0.3%)		27/8696 (0.3%)		18/8737 (0.2%)
Cardiovascular-other	9/8752 (0.1%)		12/8702 (0.1%)		17/8696 (0.2%)		14/8737 (0.2%)
Conduction abnormality/block	0/8752 (0%)		1/8702 (0%)		1/8696 (0%)		0/8737 (0%)
LVEF decrease/CHF	9/8752 (0.1%)		2/8702 (0%)		1/8696 (0%)		4/8737 (0%)
Supraventricular arrhythmia	3/8752 (0%)		0/8702 (0%)		3/8696 (0%)		1/8737 (0%)
Ventricular arrhythmia	2/8752 (0%)		2/8702 (0%)		8/8696 (0.1%)		3/8737 (0%)
Eye disorders
Eye-other	0/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Vision,NOS	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Gastrointestinal disorders
Dyspepsia/heartburn	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
GI-other	0/8752 (0%)		1/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Melena/ GI bleeding	1/8752 (0%)		1/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Rectal bleeding/hematochezia	0/8752 (0%)		1/8702 (0%)		1/8696 (0%)		0/8737 (0%)
General disorders
Constitutional symptoms-other	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Hemorrhage w/o 3-4 thrombocyt	0/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Pain-other	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Reportable adverse event, NOS	11/8752 (0.1%)		10/8702 (0.1%)		17/8696 (0.2%)		19/8737 (0.2%)
Hepatobiliary disorders
Liver-clinical	0/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Liver-other	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Infections and infestations
Respiratory infect w/o neutrop	2/8752 (0%)		1/8702 (0%)		1/8696 (0%)		1/8737 (0%)
Respiratory infection, unk ANC	0/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Urinary tr infect w/o neutrop	0/8752 (0%)		1/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Injury, poisoning and procedural complications
Surgery-hemorrhage	0/8752 (0%)		0/8702 (0%)		2/8696 (0%)		0/8737 (0%)
Investigations
Weight gain	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Metabolism and nutrition disorders
Hyperglycemia	0/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Myalgia/arthralgia, NOS	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second primary	4/8752 (0%)		5/8702 (0.1%)		2/8696 (0%)		3/8737 (0%)
Nervous system disorders
CNS hemorrhage	8/8752 (0.1%)		8/8702 (0.1%)		3/8696 (0%)		9/8737 (0.1%)
Cerebrovascular ischemia	7/8752 (0.1%)		17/8702 (0.2%)		10/8696 (0.1%)		8/8737 (0.1%)
Cranial neuropathy	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Headache	0/8752 (0%)		1/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Neuro-other	1/8752 (0%)		0/8702 (0%)		2/8696 (0%)		0/8737 (0%)
Seizures	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Sensory neuropathy	0/8752 (0%)		1/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Syncope	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		1/8737 (0%)
Tremor	0/8752 (0%)		1/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Renal and urinary disorders
Renal failure	1/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Urinary retention	1/8752 (0%)		1/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Reproductive system and breast disorders
Erectile impotence	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Respiratory, thoracic and mediastinal disorders
ARDS	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Dyspnea	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		1/8737 (0%)
Emphysema/COPD	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Epistaxis	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Pulmonary fibrosis	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Rash/desquamation	0/8752 (0%)		1/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Urticaria	0/8752 (0%)		0/8702 (0%)		1/8696 (0%)		0/8737 (0%)
Vascular disorders
Aortic Stenosis	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Cardiomyopathy	0/8752 (0%)		0/8702 (0%)		0/8696 (0%)		1/8737 (0%)
Carotid stenosis	0/8752 (0%)		2/8702 (0%)		0/8696 (0%)		2/8737 (0%)
Hypertension	2/8752 (0%)		1/8702 (0%)		0/8696 (0%)		2/8737 (0%)
Hypotension	1/8752 (0%)		0/8702 (0%)		0/8696 (0%)		0/8737 (0%)
Peripheral arterial ischemia	1/8752 (0%)		1/8702 (0%)		1/8696 (0%)		1/8737 (0%)
Thrombosis/embolism	2/8752 (0%)		2/8702 (0%)		3/8696 (0%)		4/8737 (0%)
Other (Not Including Serious) Adverse Events
	Selenium Alone		Combination		Placebo		Vitamin E Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2605/8752 (29.8%)		2550/8702 (29.3%)		2421/8696 (27.8%)		2553/8737 (29.2%)
Cardiac disorders
Cardiac ischemia/infarction	558/8752 (6.4%)		533/8702 (6.1%)		529/8696 (6.1%)		551/8737 (6.3%)
Gastrointestinal disorders
Halitosis	523/8752 (6%)		555/8702 (6.4%)		447/8696 (5.1%)		517/8737 (5.9%)
General disorders
Fatigue/malaise/lethargy	698/8752 (8%)		657/8702 (7.5%)		632/8696 (7.3%)		660/8737 (7.6%)
Skin and subcutaneous tissue disorders
Dermatitis	647/8752 (7.4%)		593/8702 (6.8%)		554/8696 (6.4%)		627/8737 (7.2%)
Nail changes	1129/8752 (12.9%)		1080/8702 (12.4%)		1072/8696 (12.3%)		1070/8737 (12.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.