Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Arizona Cancer Center at University of Arizona Health Sciences Center

M. Peter Lance

Principal Investigator

Liane Fales, RN		Ph: 602-264-4461
		Email: lfales@email.arizona.edu

U.S.A.
Arizona
	Phoenix
	Veterans Affairs Medical Center - Phoenix
		Liane Fales, RN	Ph: 602-264-4461
		Michelle Young, MD	Principal Investigator
	Scottsdale
	Mayo Clinic Scottsdale
		Narcelle Jean-Louis	Ph: 480-301-4714
		Russell Heigh, MD	Principal Investigator
	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
		Amy Carrier, RN	Ph: 520-318-7113
			Email: acarrier@azcc.arizona.edu
		Kelly Kaltenhauser, RN	Ph: 520-318-7113
			Email: kkaltenhauser@azcc.arizona.edu
		M. Peter Lance, MD	Principal Investigator
Colorado
	Denver
	University of Colorado Cancer Center at UC Health Sciences Center
		Theresa Dunn	Ph: 888-336-8262 Ext.3438
			Email: theresa.dunn@ucdenver.edu
		Dennis Ahnen, MD	Principal Investigator
New York
	Williamsville
	Endoscopy Center of Western New York
		Pat Graham, RN	Ph: 706-332-2203
			Email: pgraham@ecwny.com
		David Fay, MD	Principal Investigator
Texas
	Dallas
	Baylor University Medical Center - Dallas
		Millie Arnold, RN	Ph: 214-820-2691
			Email: MildredA@BaylorHealth.edu
		Richard Boland, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00078897
Information obtained from ClinicalTrials.gov on November 20, 2012

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