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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
University of Texas Medical School at Houston
Houston, Texas, United States
Toxicity
Time frame: 3 months
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Enrollment
22