Colorectal CancerPhase 3NCT00078897
Selenium for Prevention of Adenomatous Colorectal Polyps
A Phase 3 study testing Selenium in people with Colorectal Cancer and Adenomatous Colorectal Polyps, run by University of Arizona at 7 sites in United States.
Trial summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Selenium may be effective in preventing the recurrence of adenomatous colorectal polyps. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer, Adenomatous Colorectal Polyps, Precancerous Condition
- What is being tested?
- Selenium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,621 participants
- Where
- 7 sitesUnited States
- Study dates
- 20 Jan 2005to 17 May 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal adenomatous polyps
- Meets the following criteria by colonoscopy (performed within the past 6 months):
- Cecum was totally visualized or reached
- At least 90% visualization of colon surface area
- Removed at least 1 adenomatous polyp of at least 3 mm in size during procedure (For the Advanced Adenoma Sub-study: Removal of at least 1 advanced colorectal adenomatous polyp during procedure. An adenoma is considered advanced if it is 10 mm or greater in size, and/or has villous histology and/or shows high grade dysplasia)
- Removed no more than 10 adenomatous polyps of any size by endoscopy
- All other neoplastic and non-neoplastic colon polyps must have been completely removed (except for diminutive [less than 3 mm] sessile rectal polyps)
- For the sub-study, at least 1 advanced adenomatous polyp defined as 10 mm or greater in size and/or has villous histology and/or shows high grade dysplasia
- No prior diagnosis of any of the following:
- Colorectal cancer
- Familial adenomatous polyposis
- Ulcerative colitis
- Crohn's disease
- Hereditary non-polyposis colon cancer (HNPCC), defined as:
- Histologically confirmed colorectal cancer in at least 3 relatives, 1 of whom is a first-degree relative of the other 2
- Disease occurrence in at least 2 consecutive generations
- Colorectal cancer diagnosis in at least 1 family member who is less than 50 years of age
- Patients with a family history of colorectal cancer but who are not diagnosed with HNPCC are allowed
- No more than 1 prior segmental colon resection
PATIENT CHARACTERISTICS:
Age
- 40 to 80
Performance status
- SWOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Hemoglobin > 11 g/dL
- WBC 3,000 - 11,000/mm^3
Hepatic
- AST and ALT < 2 times upper limit of normal
- Bilirubin < 2.0 mg/dL
Renal
- Creatinine < 1.9 mg/dL
Cardiovascular
- No unstable* cardiac disease despite medication (e.g., diuretics or digitalis)
- No uncontrolled hypertension (i.e., systolic blood pressure ≥ 170 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg) despite medication NOTE: *Unstable defined as unable to walk across the room without chest pain or shortness of breath
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception for at least 2 months before and during study treatment
- Resident of a clinical center metropolitan area or obtaining regular health care in a clinical metropolitan area for at least 6 months out of the year
- Must be able to swallow pills
- No unexpected weight loss of 10% or more within the past 6 months
- No prior rheumatoid arthritis
- No poorly controlled diabetes mellitus despite medication, defined as:
- Blood sugar level ≥ 200 mg/dL on more than half of the readings taken within the past month
- No invasive malignancy within the past 5 years that required medical excision, radiotherapy, or chemotherapy except basal cell or squamous cell carcinoma
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent drugs that regulate the immune system
Chemotherapy
- No concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No concurrent radiotherapy
Surgery
- See Disease Characteristics
Other
- Prior enrollment in another adenoma prevention study allowed
- Concurrent routine aspirin (≤ 81 mg/day) allowed
- No regular use of non-steroidal anti-inflammatory drugs (NSAIDs)
- No concurrent enrollment in another research study using pharmacological cancer drugs, a cyclo-oxygenase-2 inhibitor, or selenium
- No other concurrent selenium unless dosage is ≤ 50 µg/day
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Baylor University Medical Center - Dallas
Dallas, Texas, 75246
University of Colorado Cancer Center at UC Health Sciences Center
Denver, Colorado, 80220
Veterans Affairs Medical Center - Phoenix
Phoenix, Arizona, 85012
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Scottsdale, Arizona, 85258-4512
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5499
Arizona Cancer Center - Tucson Clinic
Tucson, Arizona, 85724-5024
Endoscopy Center of Western New York
Williamsville, New York, 14221
About this study
Official title: Phase III Study of the Effects of Selenium on Adenomatous Polyp Recurrence
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Selenium may be effective in preventing the recurrence of adenomatous colorectal polyps.
PURPOSE: This randomized phase III trial is studying selenium to see how well it works in preventing the recurrence of polyps in patients with adenomatous colorectal polyps.
Read the detailed description
OBJECTIVES:
Primary
- Compare the effects of selenium vs placebo on the recurrence of adenomatous colorectal polyps, in terms of histologic type, degree of dysplasia, number, size, and location, in patients with adenomatous colorectal polyps.
- Compare the type, incidence, and outcome of side effects in patients treated with these regimens.
- Determine patient adherence to long-term treatment with these regimens.
Secondary
- Determine the effects of regimen modification by baseline blood selenium level, low-dose aspirin, selenoprotein genetic marker polymorphisms (e.g., GPx-1, GPx-2, and SEP15)
- Determine the effects of low-dose aspirin (81 mg/day) modification by ornithine decarboxylase promoter genotype, and toxicity by slow-metabolizer genotypes of the cytochrome p450 2C9 and UT1A6 loci in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to use of low-dose (≤ 81 mg/day) aspirin (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral selenium once daily.
- Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for up to 5 years* in the absence of disease progression or unacceptable toxicity.
Patients undergo follow-up colonoscopy approximately 5 years* after baseline colonoscopy.
NOTE: Some patients will continue participation for up to 7 and a half years
PROJECTED ACCRUAL: A total of 1,600 patients with an adenoma will be randomized to this study, followed by a second group of randomization of 200 patients with at least one advanced adenoma (at baseline) for a substudy. Total planned randomizations = 1,800 participants.
- Being tested
- Selenium
- Keywords
- colon cancer, rectal cancer, colorectal cancer, adenomatous polyp
- Medical subject headings
- Colorectal Neoplasms, Precancerous Conditions, Colonic Neoplasms, Rectal Neoplasms, Adenomatous Polyps
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SeleniumDrug
Also called SelenoExcell
Participants will be randomized either to selenium or placebo, taking the randomized intervention for 3 to 5 years, depending on when their recommended follow up colonoscopy is scheduled.
| Study group | Role | What they receive |
|---|---|---|
| Selenium | Active comparator | Participants receive oral selenium 200 mcg once daily. Receives: Drug: Selenium |
| Placebo | Placebo comparator | Participants receive oral placebo once daily. Receives: Drug: Selenium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Recurrent Adenomas at Surveillance Colonoscopy
Detection of metachronous colorectal adenomas during follow-up, by treatment, in the original cohort. Surveillance colonoscopy is recommended 3 to 5 years after removal of colorectal adenoma(s). Participants will remain on the study intervention until their surveillance colonoscopy. Surveillance colonoscopy is determined by participants' GI physician.
Measured: 3 to 5 years after baseline colonoscopy
Median Selenium Blood Levels at One Year.
Adequate adherence to long-term selenium treatment as measured by blood selenium levels (ng/mL) at one year.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2004 (estimated)
- Study start20 Jan 2005
- Primary completion7 Jan 2014
- Study completion17 May 2018
Why it stopped: Concluded - Terminated by PI
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,621 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- M. Peter Lance, MD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00078897
- Sponsor's protocol ID
- CDR0000353185
- Other IDs
- P30CA023074, P01CA041108
- Status last verified
- Sep 2019
- First submitted
- 8 Mar 2004
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Trejo MJ, Batai K, Chen Y, Brezina S, Chow HS, Ellis N, Lance P, Hsu CH, Pogreba-Brown K, Bishop M, Gsur A, Jacobs ET. Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial. Nutr Cancer. 2023;75(1):143-153. doi: 10.1080/01635581.2022.2096910. Epub 2022 Jul 9.
PubMed 35815403Jacobs ET, Lance P, Mandarino LJ, Ellis NA, Chow HS, Foote J, Martinez JA, Hsu CP, Batai K, Saboda K, Thompson PA. Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ Open Diabetes Res Care. 2019 Feb 7;7(1):e000613. doi: 10.1136/bmjdrc-2018-000613. eCollection 2019.
PubMed 30899530Thompson P, Roe DJ, Fales L, Buckmeier J, Wang F, Hamilton SR, Bhattacharyya A, Green S, Hsu CH, Chow HH, Ahnen DJ, Boland CR, Heigh RI, Fay DE, Martinez ME, Jacobs E, Ashbeck EL, Alberts DS, Lance P. Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention. Cancer Prev Res (Phila). 2012 Dec;5(12):1381-93. doi: 10.1158/1940-6207.CAPR-12-0204. Epub 2012 Oct 11.
PubMed 23060037Solomon SD, Wittes J, Finn PV, Fowler R, Viner J, Bertagnolli MM, Arber N, Levin B, Meinert CL, Martin B, Pater JL, Goss PE, Lance P, Obara S, Chew EY, Kim J, Arndt G, Hawk E; Cross Trial Safety Assessment Group. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. 2008 Apr 22;117(16):2104-13. doi: 10.1161/CIRCULATIONAHA.108.764530. Epub 2008 Mar 31.
PubMed 18378608
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of the Effects of Selenium on Adenomatous Polyp Recurrence
- ClinicalTrials.gov ID
- NCT00078897
- Acronym / sponsor ID
- CDR0000353185
- Keywords
- colon cancer, rectal cancer, colorectal cancer, adenomatous polyp
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Concluded - Terminated by PI
- Enrolment
- 1,621 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 20 Jan 2005 (actual)
- Primary completion
- 7 Jan 2014 (actual)
- Study completion
- 17 May 2018 (actual)
- First posted
- 9 Mar 2004 (estimated)
- Results
- Posted 24 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Selenium may be effective in preventing the recurrence of adenomatous colorectal polyps.
PURPOSE: This randomized phase III trial is studying selenium to see how well it works in preventing the recurrence of polyps in patients with adenomatous colorectal polyps.
Detailed description
OBJECTIVES:
Primary
- Compare the effects of selenium vs placebo on the recurrence of adenomatous colorectal polyps, in terms of histologic type, degree of dysplasia, number, size, and location, in patients with adenomatous colorectal polyps.
- Compare the type, incidence, and outcome of side effects in patients treated with these regimens.
- Determine patient adherence to long-term treatment with these regimens.
Secondary
- Determine the effects of regimen modification by baseline blood selenium level, low-dose aspirin, selenoprotein genetic marker polymorphisms (e.g., GPx-1, GPx-2, and SEP15)
- Determine the effects of low-dose aspirin (81 mg/day) modification by ornithine decarboxylase promoter genotype, and toxicity by slow-metabolizer genotypes of the cytochrome p450 2C9 and UT1A6 loci in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to use of low-dose (≤ 81 mg/day) aspirin (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral selenium once daily.
- Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for up to 5 years* in the absence of disease progression or unacceptable toxicity.
Patients undergo follow-up colonoscopy approximately 5 years* after baseline colonoscopy.
NOTE: Some patients will continue participation for up to 7 and a half years
PROJECTED ACCRUAL: A total of 1,600 patients with an adenoma will be randomized to this study, followed by a second group of randomization of 200 patients with at least one advanced adenoma (at baseline) for a substudy. Total planned randomizations = 1,800 participants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Selenium | Active comparator | Drug: SeleniumParticipants receive oral selenium 200 mcg once daily. |
| Placebo | Placebo comparator | Drug: SeleniumParticipants receive oral placebo once daily. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SeleniumAlso: SelenoExcellParticipants will be randomized either to selenium or placebo, taking the randomized intervention for 3 to 5 years, depending on when their recommended follow up colonoscopy is scheduled. | Drug | Placebo, Selenium |
Primary outcome
Number of Recurrent Adenomas at Surveillance Colonoscopy
Time frame: 3 to 5 years after baseline colonoscopy
Detection of metachronous colorectal adenomas during follow-up, by treatment, in the original cohort. Surveillance colonoscopy is recommended 3 to 5 years after removal of colorectal adenoma(s). Participants will remain on the study intervention until their surveillance colonoscopy. Surveillance colonoscopy is determined by participants' GI physician.
Median Selenium Blood Levels at One Year.
Time frame: One year
Adequate adherence to long-term selenium treatment as measured by blood selenium levels (ng/mL) at one year.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35815403Trejo MJ, Batai K, Chen Y, Brezina S, Chow HS, Ellis N, Lance P, Hsu CH, Pogreba-Brown K, Bishop M, Gsur A, Jacobs ET. Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial. Nutr Cancer. 2023;75(1):143-153. doi: 10.1080/01635581.2022.2096910. Epub 2022 Jul 9.
- Derived from this study: PubMed 30899530Jacobs ET, Lance P, Mandarino LJ, Ellis NA, Chow HS, Foote J, Martinez JA, Hsu CP, Batai K, Saboda K, Thompson PA. Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ Open Diabetes Res Care. 2019 Feb 7;7(1):e000613. doi: 10.1136/bmjdrc-2018-000613. eCollection 2019.
- Derived from this study: PubMed 23060037Thompson P, Roe DJ, Fales L, Buckmeier J, Wang F, Hamilton SR, Bhattacharyya A, Green S, Hsu CH, Chow HH, Ahnen DJ, Boland CR, Heigh RI, Fay DE, Martinez ME, Jacobs E, Ashbeck EL, Alberts DS, Lance P. Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention. Cancer Prev Res (Phila). 2012 Dec;5(12):1381-93. doi: 10.1158/1940-6207.CAPR-12-0204. Epub 2012 Oct 11.
- Derived from this study: PubMed 18378608Solomon SD, Wittes J, Finn PV, Fowler R, Viner J, Bertagnolli MM, Arber N, Levin B, Meinert CL, Martin B, Pater JL, Goss PE, Lance P, Obara S, Chew EY, Kim J, Arndt G, Hawk E; Cross Trial Safety Assessment Group. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. 2008 Apr 22;117(16):2104-13. doi: 10.1161/CIRCULATIONAHA.108.764530. Epub 2008 Mar 31.
- Journal ArticleLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
M. Peter Lance, MD principal investigator
University of Arizona
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Selenium in people with Colorectal Cancer and Adenomatous Colorectal Polyps, run by University of Arizona at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Recurrent Adenomas at Surveillance Colonoscopy (time frame: 3 to 5 years after baseline colonoscopy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00078897, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2019.