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



Status:Completed
Conditions:Colorectal Cancer, Cancer, Cancer, Cancer, Gastrointestinal
Therapuetic Areas:Gastroenterology, Oncology
Healthy:No
Age Range:10 - 14
Updated:11/9/2018
Start Date:November 21, 2002
End Date:April 21, 2006

Use our guide to learn which trials are right for you!

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

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.

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.

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
We found this trial at
4
sites
6621 Fannin St
Houston, Texas 77030
(832) 824-1000
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
?
mi
from
Houston, TX
Click here to add this to my saved trials
2010 E 90th St
Cleveland, Ohio 44195
(866) 223-8100
Cleveland Clinic Taussig Cancer Center At Taussig Cancer Institute, more than 250 highly skilled doctors,...
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
?
mi
from
Houston, TX
Click here to add this to my saved trials
?
mi
from
Houston, TX
Click here to add this to my saved trials