Selenium for Prevention of Adenomatous Colorectal Polyps

September 3, 2019 updated by: University of Arizona

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

1621

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85012
        • Veterans Affairs Medical Center - Phoenix
      • Scottsdale, Arizona, United States, 85259-5499
        • Mayo Clinic Scottsdale
      • Scottsdale, Arizona, United States, 85258-4512
        • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
      • Tucson, Arizona, United States, 85724-5024
        • Arizona Cancer Center - Tucson Clinic
    • Colorado
      • Denver, Colorado, United States, 80220
        • University of Colorado Cancer Center at UC Health Sciences Center
    • New York
      • Williamsville, New York, United States, 14221
        • Endoscopy Center of Western New York
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center - Dallas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Selenium
Participants receive oral selenium 200 mcg once daily.
Drug: Selenium
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.
Other Names:
  • SelenoExcell
PLACEBO_COMPARATOR: Placebo
Participants receive oral placebo once daily.
Drug: Selenium
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.
Other Names:
  • SelenoExcell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 to 5 years after baseline colonoscopy
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.
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arizona

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 20, 2005

Primary Completion (ACTUAL)

January 7, 2014

Study Completion (ACTUAL)

May 17, 2018

Study Registration Dates

First Submitted

March 8, 2004

First Submitted That Met QC Criteria

March 8, 2004

First Posted (ESTIMATE)

March 9, 2004

Study Record Updates

Last Update Posted (ACTUAL)

September 24, 2019

Last Update Submitted That Met QC Criteria

September 3, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000353185
  • P30CA023074 (U.S. NIH Grant/Contract)
  • P01CA041108 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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