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

NCT ID: NCT00685568

Last Updated: 2018-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-11-21
• Study Completion Date: 2006-04-21

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.

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.

Conditions

Colorectal Cancer; Precancerous Condition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Arm I

Patients receive oral celecoxib twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

celecoxib

Intervention Type: DRUG

Orally, twice daily for 3 months; 50 mg tablets. Celecoxib escalating doses starting at 4 mg/kg/day.

Arm II

Patients receive oral placebo twice daily for 3 months in the absence of disease progression or unacceptable toxicity.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Orally, twice daily for 3 months

Interventions

celecoxib

Orally, twice daily for 3 months; 50 mg tablets. Celecoxib escalating doses starting at 4 mg/kg/day.

Intervention Type: DRUG

placebo

Orally, twice daily for 3 months

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick M. Lynch, MD, JD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

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

Countries

United States

References

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/ajg.2009.758. Epub 2010 Mar 16.

Reference Type: RESULT

PMID: 20234350 (View on PubMed)

Other Identifiers

MDA-ID-02090

Identifier Type: -

Identifier Source: secondary_id

CDR0000596468

Identifier Type: OTHER

Identifier Source: secondary_id

ID02-090

Identifier Type: -

Identifier Source: org_study_id