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Colon CancerPhase 3NCT00005094

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

A Phase 3 study testing celecoxib in people with Colon Cancer and Rectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 30 years and older
Conditions the study is for
Colon Cancer, Rectal Cancer
What is being tested?
celecoxib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,170 participants
Where
1 siteUnited States
Study dates
Mar 2000to Apr 2006
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 38Show fewer
  • 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
  • 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-year post-treatment safety assessment
  • Subjects must meet all of the following inclusion criteria to be eligible for enrollment 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 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
  • Inclusion Criteria for Post-treatment Follow-up Colonoscopy:
  • All Subjects who completed Year 3 colonoscopy will be eligible for a post-treatment follow up colonoscopy 2 years after Year 3 colonoscopy
  • Subjects must meet all of the following inclusion criteria to be eligible for follow up 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Prevention of Sporadic Colorectal Adenomas With Celecoxib

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

Being tested
celecoxib, placebo
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • celecoxibDrug

    Also called Celebrex, SC-58635

    Given orally

  • placeboOther

    Also called PLCB

    Given orally

Study groups in NCT00005094
Study groupRoleWhat they receive
Arm I (celecoxib)ExperimentalPatients receive celecoxib twice a day for 3 years.
Receives: Drug: celecoxib
Arm II (placebo)Placebo comparatorPatients receive placebo twice a day for 3 years.
Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Year 3 (cumulative for year one and year three)

  2. 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.

    Measured: Year 5

Secondary outcomes (8)

  1. The number of adenomas identified per patient

    Will be compared between the Celecoxib treated arm and the Placebo treated arm using nonparametric analogs of the t-test (Wilcoxon rank sum or similar statistics). Poisson regression will also be used to assess whether the number of adenomas detected at surveillance colonoscopy differs between the celecoxib and placebo groups.

    Measured: Year 1

  2. The number of adenomas identified per patient

    Will be compared between the Celecoxib treated arm and the Placebo treated arm using nonparametric analogs of the t-test (Wilcoxon rank sum or similar statistics). Poisson regression will also be used to assess whether the number of adenomas detected at surveillance colonoscopy differs between the celecoxib and placebo groups.

    Measured: Year 3

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

    Will be analyzed using ordinal categorical data analysis methods.

    Measured: Up to 3 years

  4. 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

    Measured: Up to 3 years

  5. Adenoma findings at year 1 colonoscopy as predictors of adenoma findings at year 3 colonoscopy

    The findings of the Year 1 surveillance colonoscopy will also be evaluated as whether they can be used in future studies as a surrogate endpoint for the primary outcomeof the cumulative percentage of patients with newly detected adenomas at either the year one and/or at the Year 3 colonoscopy surveillance.

    Measured: Year 3

  6. Adverse events will be coded using the MedRA dictionary

    The safety analyses will consist of displays of the distribution by treatment group and adverse event category of the numbers of subjects reporting at least one episode of a specific adverse event (incidence table) and the severity and attribution to study drug of each episode reported (severity and attribution table). The proportion of subjects withdrawn due to adverse events will also be summarized.

    Measured: Up to 3 months post-treatment

  7. Mean number of adenomas detected at year 5, as well as the distribution of number of adenomas, and the adenoma burden based on the sum of the adenoma diameters at year 5

    Measured: Year 5

  8. Adverse events coded using the MedRA dictionary

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2003 (estimated)
  2. Study startMar 2000
  3. Primary completionApr 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00005094
Sponsor's protocol ID
NCI-2012-02327
Other IDs
98-008, NYH-CMC-0298-108, SC-IQ4-99-02-005, CDR0000067750, NCI-P00-0141, STRANG-98-008, BWH-NO1-CN-95015, N01CN95015
Status last verified
Apr 2013
First submitted
6 Apr 2000
Last updated
12 Apr 2013
Results posted
No

Publications

  • 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.

    PubMed 22386831

  • 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.

    PubMed 21816845

  • 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.

    PubMed 16943400

  • 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.

    PubMed 16943394

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing celecoxib in people with Colon Cancer and Rectal Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of subjects with newly detected adenomas, and will be estimated using the life table method for each treatment group (time frame: Year 3 (cumulative for year one and year three)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00005094, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2013.

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