Selenium for Prevention of Adenomatous Colorectal Polyps

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00078897
First received: March 8, 2004
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Adenomatous Colorectal Polyps
Precancerous Condition
Drug: Selenium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase III Study of the Effects of Selenium on Adenomatous Polyp Recurrence

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Recurrence of colorectal adenomatous polyps in relation to histologic type, degree of dysplasia, number, size, and location. [ Time Frame: 3 to 5 years after baseline colonoscopy ] [ Designated as safety issue: No ]
    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 and recurrence will be assessed per measurements above. Surveillance colonoscopy is determined by participants GI physician.

  • Tolerance and adequate adherence to long-term selenium treatment as measured by adverse events, serious adverse events, every 3-4 months during treatment, and laboratory values at the beginning of the study, 6 months and annually thereafter. [ Time Frame: Monitoried for 3 to 5 years after baseline colonoscopy ] [ Designated as safety issue: Yes ]

    Safety information is gathered at each study visit while participant remain on the study intervention until their surveillance colonoscopy.

    Safety Issue?: (FDAAA) Yes



Secondary Outcome Measures:
  • To investigate effect modification of the selenium intervention by baseline blood selenium level, by low-dose aspirin (81 mg/day), by selenoprotein genetic marker polymorphisms (GPx-1, GPx-2 and SEP15). [ Time Frame: 3 to 5 years after baseline colonoscopy ] [ Designated as safety issue: No ]
  • To investigate effect modification of low-dose aspirin (81 mg/day) by ornithine decarboxylase promoter genotype and effect modification of low-dose aspirin and its toxicity by slow-metabolizer genotypes of the cytochrome p450 2C9 and UGT1A6 loci. [ Time Frame: 3 to 5 years after baseline colonoscopy ] [ Designated as safety issue: No ]

Estimated Enrollment: 1800
Study Start Date: January 2001
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: SelenoExcell

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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078897

Locations
United States, Arizona
Veterans Affairs Medical Center - Phoenix
Phoenix, Arizona, United States, 85012
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Scottsdale, Arizona, United States, 85258-4512
Arizona Cancer Center - Tucson Clinic
Tucson, Arizona, United States, 85724-5024
United States, Colorado
University of Colorado Cancer Center at UC Health Sciences Center
Denver, Colorado, United States, 80220
United States, New York
Endoscopy Center of Western New York
Williamsville, New York, United States, 14221
United States, Texas
Baylor University Medical Center - Dallas
Dallas, Texas, United States, 75246
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: M. Peter Lance, MD University of Arizona
  More Information

Additional Information:
No publications provided by University of Arizona

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00078897     History of Changes
Other Study ID Numbers: CDR0000353185, P30CA023074, P01CA041108
Study First Received: March 8, 2004
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
colon cancer
rectal cancer
colorectal cancer
adenomatous polyp

Additional relevant MeSH terms:
Colorectal Neoplasms
Polyps
Precancerous Conditions
Adenomatous Polyps
Colonic Polyps
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pathological Conditions, Anatomical
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Polyps
Selenium
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on April 22, 2014