Selenium for Prevention of Adenomatous Colorectal Polyps

University of Arizona

Status and phase

Terminated

Phase 3

Conditions

Precancerous Condition

Adenomatous Colorectal Polyps

Colorectal Cancer

Treatments

Drug: Selenium

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00078897

P01CA041108 (U.S. NIH Grant/Contract)

P30CA023074 (U.S. NIH Grant/Contract)

CDR0000353185

Details and patient eligibility

About

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.

Full 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.

Enrollment

1,621 patients

Sex

All

Ages

40 to 80 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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