Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Selenium in Treating Patients With Adenomatous Colorectal Polyps

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Prevention Active 40 to 80 NCI UARIZ-00-0430-01 UARIZ-HSC-00142, NCT00078897

Special Category: NCI Web site featured trial

Objectives

Primary

1. 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.
2. Compare the type, incidence, and outcome of side effects in patients treated with these regimens.
3. Determine patient adherence to long-term treatment with these regimens.

Secondary

1. 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)
2. 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.

Entry 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
  • 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)
  • Patients accrued for the substudy must have at least 1 advanced adenomatous polyp defined as 10 mm or greater in size and/or villous histology and/or 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

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

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/mm³

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

Expected Enrollment

A total of 1,850 patients will be accrued for this study followed by a second accrual of 200 patients with advanced adenoma for a substudy.

Outcomes

Recurrence rate and size of colorectal polyps reduction as measured by colonoscopy after 3-5 year of study treatment

Tolerance and adequate adherence to long term selenium treatment as measured by adverse events, serious adverse events, and laboratory values every 3-4 months during treatment, and 1 month after study completion

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 periodically for approximately 5 years* after baseline colonoscopy.

 [Note: Some patients will continue participation for up to 7.6 years]

Trial Contact Information

Trial Lead Organizations

Arizona Cancer Center at University of Arizona Health Sciences Center

M. Peter Lance, MD, Principal investigator		Ph: 520-626-4492; 800-622-2673 Email: plance@azcc.arizona.edu

U.S.A.
Arizona
	Phoenix
	Veterans Affairs Medical Center - Phoenix
		Francisco Ramirez, MD	Ph:  602-264-4461 800-554-7174
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
		Liane Fales, RN	Ph:  602-264-4461
			Email: lfales@email.arizona.edu
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Clinical Trials Office - Arizona Cancer Center at University of Arizona Health Sciences Center	Ph:  520-626-9008
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Dennis Ahnen, MD	Ph:  303-399-8020 x3018
Texas
	Dallas
	Baylor University Medical Center - Dallas
		Clinical Trials Office - Baylor University Medical Center - Dallas	Ph:  800-422-9567

Related Information

Featured trial article

Registry Information
Official Title		Phase III Study of the Effects of Selenium on Adenomatous Polyp Recurrence
Trial Start Date		2001-01-15
Trial Completion Date		2013-03-01 (estimated)
Registered in ClinicalTrials.gov		NCT00078897
Date Submitted to PDQ		2004-01-14
Information Last Verified		2008-09-17
NCI Grant/Contract Number		CA23074, CA41108