Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps

NCT00005094 | Completed Phase 3

• 9 other identifiers: NCI-2012-0232798-008NYH-CMC-0298-108SC-IQ4-99-02-005CDR0000067750NCI-P00-0141STRANG-98-008BWH-NO1-CN-95015N01CN95015
• Study Type: interventional
• Target: 1,170
• Locations: 1 country
• Sites: 1

Brief Summary

Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. The use of celecoxib has been approved for use in reducing the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP). It is not known whether there is a clinical benefit from a reduction in the number of colorectal polyps in FAP patients. The use of celecoxib may be an effective way to prevent the development of sporadic adenomatous polyps, precursors of colorectal cancer. This randomized phase III trial is studying celecoxib to see how well it works compared to a placebo in preventing the development of adenomatous colorectal polyps in patients who have had at least one polyp removed.

Conditions

Colon Cancer; Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of subjects with newly detected adenomas, and will be estimated using the life table method for each treatment group

  Will be estimated using the life table method for each treatment group and compared using a life-table extension of the Mantel-Haenszel statistics with stratification for aspirin use. Additional analysis will be performed for the primary endpoint to adjust for the baseline prognostic factors and colon cancer/adenoma risk factors using, for example, proportional hazard model or logistic model.

  Year 3 (cumulative for year one and year three)

• Percentage of patients with adenomas, aspirin use at baseline, and covariates

  This will be derived by treatment group (celecoxib 400 mg bid, celecoxib 200 mg bid, or placebo) and low-dose aspirin use at baseline and in relationship to the patient's adenoma history at the year 3 colonoscopy. Of particular interest is whether the conditional rate of adenomas at year 5 differs by treatment group and strata with control for potential differences in these groups by adenoma history at year 3 colonoscopy, age, sex, family history of colorectal cancer, smoking, concomitant use of NSAID's, total time on study drug, and other covariates.

  Year 5

Secondary Outcomes (8)

• The number of adenomas identified per patient

  Year 1

• The number of adenomas identified per patient

  Year 3

• The highest histopathologic grade, largest size, and polyp burden (sum of the polyp diameters) of the colorectal adenomas

  Up to 3 years

• The number of advanced adenomas (adenoma of size 1.0 cm or larger, any villous histology, high grade dysplasia, or invasive cancer) detected at surveillance

  Up to 3 years

• Adenoma findings at year 1 colonoscopy as predictors of adenoma findings at year 3 colonoscopy

  Year 3

Study Arms (2)

Arm I (celecoxib)

EXPERIMENTAL

Patients receive celecoxib twice a day for 3 years.

Drug: celecoxib

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo twice a day for 3 years.

Other: placebo

Interventions

celecoxib DRUG

Given orally

Also known as: Celebrex, SC-58635

Arm I (celecoxib)

placebo OTHER

Given orally

Also known as: PLCB

Arm II (placebo)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject has had a documented colonoscopy to the cecum, by a study physician, with adequate preparation resulting in diagnosis and clearance of an adenomatous polyp(s) within 24 weeks prior to study entry; the 24- week period begins from the time of colonoscopy, which had resulted in full visualization of colon/rectum or the time of removal of adenoma which ever had occurred first
• At the baseline colonoscopy, the subject must have one of the following documented:
• One adenomatous polyp \> 6 mm;
• If the colonoscopy report says that a 6 mm polyp was removed, and the local pathology report confirms that this adenoma was AT LEAST 6mm in any dimension, the subject is eligible
• If the colonoscopy report says that the 6mm polyp was removed, and the local pathology report says that multiple fragments of adenoma were obtained, the subject is eligible
• If the colonoscopy report says that a 6mm polyp was removed, but the pathologist measured this as 5mm or less in greatest dimension, the subject is NOT eligible
• Two or more adenomatous polyps of any size documented by local pathology report plus colonoscopy report; or
• One adenomatous polyp of any size and a documented history of adenomatous polyp(s); if the colonoscopy report indicates that polyps of any size were left in the subject, the subject is NOT eligible; if the colonoscopy report says that all visible adenomas were removed, the subject is eligible.
• If the colonoscopy report does not specifically state that all visible adenomas were removed, but does not describe any adenomas that were left in, the subject is eligible
• The subject is willing to abstain from chronic use of all NSAIDs or COX-2 inhibitors, excluding aspirin (cardioprotective doses of less than or equal to 325mg po QOD or 162.5mg po QD) for the duration of the study; chronic use of NSAIDs is defined as a frequency 1 week (7 consecutive days) for more than three weeks per year
• The subject is willing to limit aspirin use to less than or equal to 325mg po QOD or 162.5mg po QD for the duration of the study
• The subset of subjects undergoing SEB analysis will be required to abstain from any aspirin use for the duration of the study
• The subjects' anticipated use of oral/intravenous corticosteroid must be less than 2 weeks over a 6 month period
• The subject's anticipated use of orally inhaled steroid must be less than 4 weeks over a 6 month period; if nasally inhaled steroid use is anticipated, the subject agrees to use mometasone (Nasonex) only. Use of mometasone is not restricted (all other nasal steroids are prohibited); subjects may change to mometasone, but must have discontinued the previous nasal steroid for at least 30 days prior to randomization
• If a subject is female and of child-bearing potential (women are considered not of childbearing potential if they are at least 2 years post-menopausal and/or surgically sterile), she:

You may not qualify if:

• The subject has a history of Familial Adenomatous Polyposis or Hereditary Non-Polyposis Colorectal Cancer (as defined by the Amsterdam Criteria)
• The subject has a history of inflammatory bowel disease
• Subject has a chronic or acute renal or hepatic disorder or a significant bleeding disorder
• The subject has a history of hypersensitivity to COX-2 inhibitors, NSAIDs, salicylates, or sulfonamides
• The subject has a history of large bowel resection, except appendectomy
• The subject has used NSAIDs, excluding aspirin at any dose at a frequency equal to or greater than three times per week during the two months prior to randomization
• The subject used aspirin at a dose exceeding 325mg QOD or 162.5mg QD at a frequency equal to or greater than three times per week during the two months prior to study entry
• For SEB measurement participants only: the subject used any dose of aspirin at a frequency greater than once weekly during the two months prior to study entry
• The subject used oral/intravenous corticosteroids for more than 2 weeks in past 6 months
• The subject used orally inhaled corticosteroids for more than 4 weeks in past 6 months and/or the subject has used nasally inhaled corticosteroids (except mometasone) within the last month prior to randomization
• The subject has treatment for a gastrointestinal ulcer in the past month prior to study entry
• The subject has a history of invasive cancer within the past five years (excluding non-melanoma skin cancer)
• The subject has received any investigational medication within 30 days prior to randomization or is scheduled to receive an investigational drug other than celecoxib during the course of the study
• The subject is unable to return for follow-up tests
• The subject participated in the study previously and had been withdrawn

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (4)

• Arber N, Lieberman D, Wang TC, Zhang R, Sands GH, Bertagnolli MM, Hawk ET, Eagle C, Coindreau J, Zauber A, Lanas A, Levin B. The APC and PreSAP trials: a post hoc noninferiority analysis using a comprehensive new measure for gastrointestinal tract injury in 2 randomized, double-blind studies comparing celecoxib and placebo. Clin Ther. 2012 Mar;34(3):569-79. doi: 10.1016/j.clinthera.2012.02.001. Epub 2012 Mar 2.

  PMID: 22386831 DERIVED

• Chan AT, Sima CS, Zauber AG, Ridker PM, Hawk ET, Bertagnolli MM. C-reactive protein and risk of colorectal adenoma according to celecoxib treatment. Cancer Prev Res (Phila). 2011 Aug;4(8):1172-80. doi: 10.1158/1940-6207.CAPR-10-0403.

  PMID: 21816845 DERIVED

• Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET; APC Study Investigators. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006 Aug 31;355(9):873-84. doi: 10.1056/NEJMoa061355.

  PMID: 16943400 DERIVED

• Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B, Eagle C, Hawk E, Lechuga M, Zauber AG, Bertagnolli MM, Arber N, Wittes J; APC and PreSAP Trial Investigators. Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation. 2006 Sep 5;114(10):1028-35. doi: 10.1161/CIRCULATIONAHA.106.636746.

  PMID: 16943394 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Monica Bertagnolli

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2000
• First Posted: November 5, 2003
• Study Start: March 1, 2000
• Primary Completion: April 1, 2006
• Last Updated: April 12, 2013

Record last verified: 2013-04

Locations

US (1)