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

study id #: NCT00685568

condition: Colorectal Cancer, Precancerous Condition

status: completed

purpose:

intervention:
Drug: celecoxib
Other: placebo

start date: November 21, 2002

estimated completion: April 21, 2006

last updated: November 7, 2018

phase of development: Phase 1

size / enrollment: 22

study design:
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention

study 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.

primary outcomes:

• Toxicity [ Time Frame:3 months ] [ Designated as safety issue: Yes ]

secondary outcomes:

• Aberrant crypt foci (ACF) and adenoma burden in the entire colorectum [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Elimination of the learning curve in a phase II/III trial [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Comparison of sedation strategies based on local standards [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Validation of technique for scoring ACFs [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Short-term (3 month) impact of celecoxib on ACF count [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Adherence [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Influence of polymorphisms on age of onset of phenotype or on the number of colorectal polyps [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Feasibility of psychosocial questionnaires [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  
• Pharmacokinetics (plasma drug trough concentrations) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

inclusion criteria:

DISEASE CHARACTERISTICS: 1.Diagnosis of familial adenomatous polyposis (FAP) based on genetic predisposition testing
2.Genotype-positive FAP (pathologic Adenomatous polyposis coli (APC) mutation)
2a.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
3. Has an intact colon
3a. No requirement for colectomy
3b. Parent(s) do not desire colectomy (regardless of adenoma burden)
4. Colorectal adenoma burden as assessed by baseline colonoscopy
4a. No diagnosis of severe dysplasia or greater
4b. No more than 10 adenomas ≥ 1 cm
4c. No more than 100 adenomas of any size
4d. No evidence of anemia (hematocrit < 33%)
5. No new diagnosis of carcinoma

PATIENT CHARACTERISTICS:
1. White Blood Count (WBC) > 3,000/μL
2. Platelet count > 100,000/μL
3. Hemoglobin > 10.0 g/dL
4. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) < 1.5 times upper limit of normal (ULN)
5. Alkaline phosphatase < 1.5 times ULN
6. Total bilirubin < 1.5 times ULN
7. Creatinine < 1.5 times ULN
8. Not pregnant or nursing
9. Negative pregnancy test
10. Fertile patients must use effective contraception
11. No history of hypersensitivity to COX-2 inhibitors, sulfonamides, NSAIDs, or salicylates
12. No history of peptic ulcer disease
13. No significant medical or psychiatric problem that, in the opinion of the principal investigator, would make the patient a poor candidate for the study
14. No other unacceptable clinical risk (e.g., previously unknown bleeding diatheses)
15. No invasive carcinoma within the past 5 years

PRIOR CONCURRENT THERAPY:
1. More than 3 months since prior investigational agent
2. More than 6 months since prior chemotherapy
3. No prior radiotherapy to the pelvis
4. At least 3 months since prior NSAIDs (at any dose) at a frequency of ≥ 3 times/week
5. At least 1 month since prior NSAIDs (at any dose) at a frequency of < 3 times/week
6. At least 1 month since prior nasal steroids
7. Concurrent Nonsteroidal Antiinflammatory Drugs (NSAIDs) allowed provided they are administered ≤ 5 times per month
8. Concurrent orally inhaled steroids allowed provided they are administered for ≤ 4 weeks over a 6-month period
9. Concurrent oral or intravenous (IV) corticosteroids allowed provided they are administered for ≤ 2 consecutive weeks over a 6-month period
10. Concurrent proton pump inhibitors to treat gastric reflux allowed
11. No concurrent nasal steroids except mometasone (Nasonex)
12. No concurrent fluconazole, lithium, or adrenocorticosteroids

exclusion criteria:

sponsor: M.D. Anderson Cancer Center

investigators: Patrick M. Lynch, MD, JD

trial center locations: United States