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

Inclusion Criteria:

• The subject has had a documented colonoscopy to the cecum, by a study physician, withadequate 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 ofcolonoscopy, which had resulted in full visualization of colon/rectum or the time ofremoval 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 localpathology report confirms that this adenoma was AT LEAST 6mm in anydimension, the subject is eligible

• If the colonoscopy report says that the 6mm polyp was removed, and the localpathology report says that multiple fragments of adenoma were obtained, thesubject is eligible

• If the colonoscopy report says that a 6mm polyp was removed, but thepathologist measured this as 5mm or less in greatest dimension, the subjectis NOT eligible

• Two or more adenomatous polyps of any size documented by local pathology reportplus colonoscopy report; or

• One adenomatous polyp of any size and a documented history of adenomatouspolyp(s); if the colonoscopy report indicates that polyps of any size were leftin the subject, the subject is NOT eligible; if the colonoscopy report says thatall visible adenomas were removed, the subject is eligible. If the colonoscopy report does not specifically state that all visible adenomas wereremoved, 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 afrequency 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 anyaspirin use for the duration of the study

• The subjects' anticipated use of oral/intravenous corticosteroid must be less than 2weeks over a 6 month period

• The subject's anticipated use of orally inhaled steroid must be less than 4 weeks overa 6 month period; if nasally inhaled steroid use is anticipated, the subject agrees touse mometasone (Nasonex) only. Use of mometasone is not restricted (all other nasalsteroids are prohibited); subjects may change to mometasone, but must havediscontinued 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 ofchildbearing potential if they are at least 2 years post-menopausal and/or surgicallysterile), she:

• Has been using adequate contraception (abstinence, IUD, birth control pills, orspermicidal gel with diaphragm or condom) since her last menses and will useadequate contraception during the study,

• Is not lactating, and

• Has a documented negative serum or negative urine pregnancy tests within 14 daysprior 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 whichtotal bilirubin must be =< 2.0 X ULN

• Inclusion Criteria for the 2-year post-treatment safety assessment:

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

• Subjects must meet all of the following inclusion criteria to be eligible forenrollment into the 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 datacollection

• The subject has signed and dated an addendum (Subject Letter) to theinformed consent document prior to performing any post-treatment safetyassessment procedures

• Inclusion Criteria for Post-treatment Follow-up Colonoscopy:

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

• Subjects must meet all of the following inclusion criteria to be eligible forfollow up colonoscopy:

• Completion of study treatment (3 years of study drug or on study drug onDecember 17, 2004) on the 3-year randomized portion of the clinical trial

• Willingness to continue with follow-up contacts every 6 months forcollecting concomitant medications use data and end-of-study colonoscopy atYear 5

• The subject has signed and dated a separate informed consent document priorto performing any follow-up procedures; while delay in obtaining consent isnot optimal, patients may be consented and entered into the post-treatmentfollow-up study at any time prior to their Year 5 colonoscopy but no laterthan 1Q2007

Exclusion Criteria:

• The subject has a history of Familial Adenomatous Polyposis or HereditaryNon-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 bleedingdisorder

• 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 orgreater 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 frequencyequal to or greater than three times per week during the two months prior to studyentry

• For SEB measurement participants only: the subject used any dose of aspirin at afrequency 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 6months

• The subject used orally inhaled corticosteroids for more than 4 weeks in past 6 monthsand/or the subject has used nasally inhaled corticosteroids (except mometasone) withinthe last month prior to randomization

• The subject has treatment for a gastrointestinal ulcer in the past month prior tostudy entry

• The subject has a history of invasive cancer within the past five years (excludingnon-melanoma skin cancer)

• The subject has received any investigational medication within 30 days prior torandomization or is scheduled to receive an investigational drug other than celecoxibduring 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 arenot appropriate candidates for Study participation

• Subjects currently using triazole or azole antifungal agents (i.e., fluconazole) orlithium