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

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00685568

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Actual Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Precancerous Condition	Drug: celecoxib Other: placebo	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Prevention

Official Title:

Phase I Pilot Toxicity/Methods Validation Study of Celecoxib in Genotype-Positive Children With Familial Adenomatous Polyposis

Actual Study Start Date :

Nov 21, 2002

Actual Primary Completion Date :

Apr 21, 2006

Actual Study Completion Date :

Apr 21, 2006

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Toxicity [3 months]

Secondary Outcome Measures

Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum [3 months]
Elimination of the learning curve in a phase II/III trial [3 months]
Comparison of sedation strategies based on local standards [3 months]
Validation of technique for scoring ACFs [3 months]
Short-term (3 month) impact of celecoxib on ACF count [3 months]
Adherence [3 months]
Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps [3 months]
Feasibility of psychosocial questionnaires [3 months]
Pharmacokinetics (plasma drug trough concentrations) [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 14 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
2	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
3	Texas Children's Hospital	Houston	Texas	United States	77030
4	University of Texas Medical School at Houston	Houston	Texas	United States	77030