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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00685568
First received: May 23, 2008
Last updated: November 16, 2012
Last verified: November 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Precancerous Condition
 Drug: celecoxib
Other: placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
Official Title: Phase I Pilot Toxicity/Methods Validation Study of Celecoxib in Genotype-Positive Children With Familial Adenomatous Polyposis

Resource links provided by NLM:

Drug Information available for: Celecoxib
U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Elimination of the learning curve in a phase II/III trial [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Comparison of sedation strategies based on local standards [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Validation of technique for scoring ACFs [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Short-term (3 month) impact of celecoxib on ACF count [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Adherence [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Feasibility of psychosocial questionnaires [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics (plasma drug trough concentrations) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: December 2002
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
 Drug: celecoxib
Orally, twice daily for 3 months; 50 mg tablets. Celecoxib escalating doses starting at 4 mg/kg/day.
Placebo Comparator: Arm II
Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.
 Other: placebo
Orally, twice daily for 3 months

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.

  Eligibility

Ages Eligible for Study:   10 Years to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00685568

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Texas Children's Hospital
Houston, Texas, United States, 77030
University of Texas Medical School at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Study Chair: Patrick M. Lynch, MD, JD M.D. Anderson Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00685568     History of Changes
Other Study ID Numbers: ID02-090, MDA-ID-02090, CDR0000596468
Study First Received: May 23, 2008
Last Updated: November 16, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
colon cancer
rectal cancer
familial adenomatous polyposis

Additional relevant MeSH terms:
Colorectal Neoplasms
Disease Susceptibility
Genetic Predisposition to Disease
Adenomatous Polyposis Coli
Precancerous Conditions
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
 Disease Attributes
Pathologic Processes
Adenomatous Polyps
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colonic Neoplasms
Neoplastic Syndromes, Hereditary
Intestinal Polyposis
Genetic Diseases, Inborn
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013