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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00685568
• Other study ID #: ID02-090
• Secondary ID: MDA-ID-02090CDR0
• Status: Completed
• Phase: Phase 1
• Start date: November 21, 2002
• Est. completion date: April 21, 2006

Study information

• Verified date: November 2018
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 21, 2006
• Est. primary completion date: April 21, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli
• Colorectal Cancer
• Colorectal Neoplasms
• Precancerous Condition
• Precancerous Conditions

Intervention

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

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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/aj — View Citation

Outcome

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