Clinical trial NCT00078897: Selenium for Prevention of Adenomatous Colorectal Polyps
Official title: Phase III Study of the Effects of Selenium on Adenomatous Polyp Recurrence
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Colorectal Cancer
Adenomatous Colorectal Polyps
Precancerous Condition
Keywords: colon cancer
rectal cancer
colorectal cancer
adenomatous polyp
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-03-09
Enrollment: 1621
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: Number of Recurrent Adenomas at Surveillance Colonoscopy
timeFrame: 3 to 5 years after baseline colonoscopy
measure: Median Selenium Blood Levels at One Year.
timeFrame: One year
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Veterans Affairs Medical Center - Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center - Tucson Clinic
state: Arizona
city: Denver
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Williamsville
country: United States
facility: Endoscopy Center of Western New York
state: New York
city: Dallas
country: United States
facility: Baylor University Medical Center - Dallas
state: Texas
Study officials:
affiliation: University of Arizona
name: M. Peter Lance, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Trejo MJ, Batai K, Chen Y, Brezina S, Chow HS, Ellis N, Lance P, Hsu CH, Pogreba-Brown K, Bishop M, Gsur A, Jacobs ET. Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial. Nutr Cancer. 2023;75(1):143-153. doi: 10.1080/01635581.2022.2096910. Epub 2022 Jul 9.
citation: Jacobs ET, Lance P, Mandarino LJ, Ellis NA, Chow HS, Foote J, Martinez JA, Hsu CP, Batai K, Saboda K, Thompson PA. Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ Open Diabetes Res Care. 2019 Feb 7;7(1):e000613. doi: 10.1136/bmjdrc-2018-000613. eCollection 2019.
citation: Thompson P, Roe DJ, Fales L, Buckmeier J, Wang F, Hamilton SR, Bhattacharyya A, Green S, Hsu CH, Chow HH, Ahnen DJ, Boland CR, Heigh RI, Fay DE, Martinez ME, Jacobs E, Ashbeck EL, Alberts DS, Lance P. Design and baseline characteristics of participants in a phase III randomized trial of celecoxib and selenium for colorectal adenoma prevention. Cancer Prev Res (Phila). 2012 Dec;5(12):1381-93. doi: 10.1158/1940-6207.CAPR-12-0204. Epub 2012 Oct 11.
citation: Solomon SD, Wittes J, Finn PV, Fowler R, Viner J, Bertagnolli MM, Arber N, Levin B, Meinert CL, Martin B, Pater JL, Goss PE, Lance P, Obara S, Chew EY, Kim J, Arndt G, Hawk E; Cross Trial Safety Assessment Group. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. 2008 Apr 22;117(16):2104-13. doi: 10.1161/CIRCULATIONAHA.108.764530. Epub 2008 Mar 31.