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Celecoxib in Preventing Colorectal Cancer in Young Patients With a Genetic Predisposition for Familial Adenomatous Polyposis

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ClinicalTrials.gov Identifier: NCT00685568
Recruitment Status : Completed
First Posted : May 28, 2008
Last Update Posted : November 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE May 23, 2008
First Posted Date  ICMJE May 28, 2008
Last Update Posted Date November 7, 2018
Actual Study Start Date  ICMJE November 21, 2002
Actual Primary Completion Date April 21, 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2012)
Toxicity [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2008)
Safety
Change History Complete list of historical versions of study NCT00685568 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2012)
  • Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum [ Time Frame: 3 months ]
  • Elimination of the learning curve in a phase II/III trial [ Time Frame: 3 months ]
  • Comparison of sedation strategies based on local standards [ Time Frame: 3 months ]
  • Validation of technique for scoring ACFs [ Time Frame: 3 months ]
  • Short-term (3 month) impact of celecoxib on ACF count [ Time Frame: 3 months ]
  • Adherence [ Time Frame: 3 months ]
  • Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps [ Time Frame: 3 months ]
  • Feasibility of psychosocial questionnaires [ Time Frame: 3 months ]
  • Pharmacokinetics (plasma drug trough concentrations) [ Time Frame: 3 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2008)
  • Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum
  • Elimination of the learning curve in a phase II/III trial
  • Comparison of sedation strategies based on local standards
  • Validation of technique for scoring ACFs
  • Short-term (3 month) impact of celecoxib on ACF count
  • Factors influencing accrual
  • Adherence
  • Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps
  • Feasibility of psychosocial questionnaires
  • Pharmacokinetics (plasma drug trough concentrations)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Celecoxib in Preventing Colorectal Cancer in Young Patients With a Genetic Predisposition for Familial Adenomatous Polyposis
Official Title  ICMJE Phase I Pilot Toxicity/Methods Validation Study of Celecoxib in Genotype-Positive Children With Familial Adenomatous Polyposis
Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of celecoxib may keep polyps and colorectal cancer from forming in patients with familial adenomatous polyposis.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of celecoxib in treating young patients with a genetic predisposition for familial adenomatous polyposis.

Detailed Description

OBJECTIVES:

Primary

  • Determine the safety and toxicity of celecoxib in pediatric patients with genotype-positive familial adenomatous polyposis.

Secondary

  • Determine the aberrant crypt foci (ACF) and adenoma burden in the entire colorectum of these patients.
  • Eliminate the learning curve in a phase II/III trial (reproducibility of endoscopic techniques, tolerability of procedure).
  • Compare sedation strategies based on local standards (monitored anesthesia care vs conscious sedation).
  • Validate the ACF scoring technique.
  • Establish the short-term (3 month) impact of celecoxib on ACF count in order to determine appropriateness of ACF as a pathologic endpoint in a phase II/III trial.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Patients undergo colonoscopy at baseline and at 3 months. Patients also complete psychosocial questionnaires at baseline.

Blood samples are collected at baseline to assess the influence of polymorphisms (CYP2C9, uridine diphosphate (UDP)-glucuronosyl transferase, A6, glutathione S-transferase [GST] M1, and Glutathione S-transferase (GST) theta 1 (GSTT1)) on age of onset of phenotype or number of colorectal polyps. Plasma drug trough levels are assessed at baseline, 1 month, and 3 months.

After completion of study treatment, patients are followed periodically for up to 2 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Condition  ICMJE
  • Colorectal Cancer
  • Precancerous Condition
Intervention  ICMJE
  • Drug: celecoxib
    Orally, twice daily for 3 months; 50 mg tablets. Celecoxib escalating doses starting at 4 mg/kg/day.
  • Other: placebo
    Orally, twice daily for 3 months
Study Arms  ICMJE
  • Experimental: Arm I
    Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
    Intervention: Drug: celecoxib
  • Placebo Comparator: Arm II
    Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
    Intervention: Other: placebo
Publications * Lynch PM, Ayers GD, Hawk E, Richmond E, Eagle C, Woloj M, Church J, Hasson H, Patterson S, Half E, Burke CA. The safety and efficacy of celecoxib in children with familial adenomatous polyposis. Am J Gastroenterol. 2010 Jun;105(6):1437-43. doi: 10.1038/ajg.2009.758. Epub 2010 Mar 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 16, 2012)
22
Original Enrollment  ICMJE
 (submitted: May 23, 2008)
18
Actual Study Completion Date  ICMJE April 21, 2006
Actual Primary Completion Date April 21, 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Diagnosis of familial adenomatous polyposis (FAP) based on genetic predisposition testing
  • Genotype-positive FAP (pathologic Adenomatous polyposis coli (APC) mutation)

    • No attenuated FAP genotype, defined by any of the following:

      • Mutation at the 5' end of APC and exon 4
      • Exon 9-associated phenotypes
      • 3' region mutations
  • Has an intact colon

    • No requirement for colectomy
    • Parent(s) do not desire colectomy (regardless of adenoma burden)
  • Colorectal adenoma burden as assessed by baseline colonoscopy

    • No diagnosis of severe dysplasia or greater
    • No more than 10 adenomas ≥ 1 cm
    • No more than 100 adenomas of any size
    • No evidence of anemia (hematocrit < 33%)
  • No new diagnosis of carcinoma

PATIENT CHARACTERISTICS:

  • White Blood Count (WBC) > 3,000/μL
  • Platelet count > 100,000/μL
  • Hemoglobin > 10.0 g/dL
  • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) < 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase < 1.5 times ULN
  • Total bilirubin < 1.5 times ULN
  • Creatinine < 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
  • No history of peptic ulcer disease
  • No significant medical or psychiatric problem that, in the opinion of the principal investigator, would make the patient a poor candidate for the study
  • No other unacceptable clinical risk (e.g., previously unknown bleeding diatheses)
  • No invasive carcinoma within the past 5 years

PRIOR CONCURRENT THERAPY:

  • More than 3 months since prior investigational agent
  • More than 6 months since prior chemotherapy
  • No prior radiotherapy to the pelvis
  • At least 3 months since prior NSAIDs (at any dose) at a frequency of ≥ 3 times/week
  • At least 1 month since prior NSAIDs (at any dose) at a frequency of < 3 times/week
  • At least 1 month since prior nasal steroids
  • Concurrent Nonsteroidal Antiinflammatory Drugs (NSAIDs) allowed provided they are administered ≤ 5 times per month
  • Concurrent orally inhaled steroids allowed provided they are administered for ≤ 4 weeks over a 6-month period
  • Concurrent oral or intravenous (IV) corticosteroids allowed provided they are administered for ≤ 2 consecutive weeks over a 6-month period
  • Concurrent proton pump inhibitors to treat gastric reflux allowed
  • No concurrent nasal steroids except mometasone (Nasonex)
  • No concurrent fluconazole, lithium, or adrenocorticosteroids
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 14 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00685568
Other Study ID Numbers  ICMJE ID02-090
MDA-ID-02090
CDR0000596468 ( Other Identifier: NCI Clinical Trials )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Patrick M. Lynch, MD, JD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP