Phase I Pilot Toxicity/Methods Validation Study of Celecoxib in Genotype-Positive Children With Familial Adenomatous Polyposis
10 Years
14 Years
Both
Colorectal Cancer, Precancerous Condition
Trial Information
Phase I Pilot Toxicity/Methods Validation Study of Celecoxib in Genotype-Positive Children With 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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention
Outcome Measure:
Toxicity
Outcome Time Frame:
3 months
Safety Issue:
Yes
Principal Investigator
Patrick M. Lynch, MD, JD
Investigator Role:
Study Chair
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
ID02-090
NCT ID:
NCT00685568
Start Date:
December 2002
Completion Date:
November 2006
Related Keywords:
- Colorectal Cancer
- Precancerous Condition
- colon cancer
- rectal cancer
- familial adenomatous polyposis
- Colorectal Neoplasms
- Adenomatous Polyposis Coli
- Precancerous Conditions
Name | Location |
|---|---|
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
| Texas Children's Hospital | Houston, Texas |
| University of Texas Medical School at Houston | Houston, Texas 77030 |
