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


Phase 1
10 Years
14 Years
Not Enrolling
Both
Colorectal Cancer, Precancerous Condition

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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 CenterCleveland, Ohio  44195
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Texas Children's HospitalHouston, Texas  
University of Texas Medical School at HoustonHouston, Texas  77030