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

NCT ID: NCT00005094

Last Updated: 2013-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31

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.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and efficacy of celecoxib in reducing the occurrence of new sporadic adenomatous polyps (SAP) in the colon and rectum in patients who have undergone polypectomy for previous SAP.

OUTLINE: This is a randomized, double blind, placebo controlled study. Patients are entered on one of two treatment arms.

Arm I: Patients receive celecoxib twice a day for 3 years.

Arm II: Patients receive placebo twice a day for 3 years.

Patients are evaluated for adenomatous colorectal polyps at 1 and 3 years.

PROJECTED ACCRUAL: Over 1000 patients will be accrued for this study.

Conditions

Colon Cancer; Rectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm I (celecoxib)

Patients receive celecoxib twice a day for 3 years.

Group Type: EXPERIMENTAL

celecoxib

Intervention Type: DRUG

Given orally

Arm II (placebo)

Patients receive placebo twice a day for 3 years.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given orally

Interventions

celecoxib

Given orally

Intervention Type: DRUG

placebo

Given orally

Intervention Type: OTHER

Other Intervention Names

Celebrex; SC-58635; PLCB

Eligibility Criteria

Inclusion Criteria

• 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:

• Has been using adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) since her last menses and will use adequate contraception during the study,
• Is not lactating, and
• Has a documented negative serum or negative urine pregnancy tests within 14 days prior to study entry
• The subject must sign and date the informed consent statement
• Hemoglobin level of greater than 11.5 (both men and women)
• WBC count greater than 3000/mm^3
• Platelet count greater than 125,000
• Creatinine =< 1.5 X ULN
• AST =< 1.5 X ULN
• ALT =< 1.5 X ULN
• Total bilirubin =< 1.5 X ULN, unless the subject has Gilbert's disease, for which total bilirubin must be =< 2.0 X ULN

• Subjects who were enrolled in the Year-3 study will be eligible for a 2-year post-treatment safety assessment

• Have been enrolled on the 3-year randomized portion of the clinical trial
• Willingness to continue with follow-up annual contacts for safety data collection
• The subject has signed and dated an addendum (Subject Letter) to the informed consent document prior to performing any post-treatment safety assessment procedures

• All Subjects who completed Year 3 colonoscopy will be eligible for a post-treatment follow up colonoscopy 2 years after Year 3 colonoscopy

• Completion of study treatment (3 years of study drug or on study drug on December 17, 2004) on the 3-year randomized portion of the clinical trial
• Willingness to continue with follow-up contacts every 6 months for collecting concomitant medications use data and end-of-study colonoscopy at Year 5
• The subject has signed and dated a separate informed consent document prior to performing any follow-up procedures; while delay in obtaining consent is not optimal, patients may be consented and entered into the post-treatment follow-up study at any time prior to their Year 5 colonoscopy but no later than 1Q2007

Exclusion Criteria

• 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
• Subjects whom, in the opinion of the Lead PI, Institutional PI, or Subinvestigator are not appropriate candidates for Study participation
• Subjects currently using triazole or azole antifungal agents (i.e., fluconazole) or lithium

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Monica Bertagnolli

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22386831 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21816845 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 16943400 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 16943394 (View on PubMed)

Other Identifiers

98-008

Identifier Type: -

Identifier Source: secondary_id

NYH-CMC-0298-108

Identifier Type: -

Identifier Source: secondary_id

SC-IQ4-99-02-005

Identifier Type: -

Identifier Source: secondary_id

CDR0000067750

Identifier Type: -

Identifier Source: secondary_id

NCI-P00-0141

Identifier Type: -

Identifier Source: secondary_id

STRANG-98-008

Identifier Type: -

Identifier Source: secondary_id

BWH-NO1-CN-95015

Identifier Type: -

Identifier Source: secondary_id

N01CN95015

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02327

Identifier Type: -

Identifier Source: org_study_id