RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of celecoxib may prevent or treat head and neck cancer.

PURPOSE: This randomized phase II trial is studying celecoxib to see how well it works compared to placebo in preventing head and neck cancer in patients with oral leukoplakia.

Condition	Treatment or Intervention	Phase
Hypopharyngeal Cancer lip and oral cavity cancer Nasopharyngeal Cancer Oropharyngeal Cancer Precancerous Condition	Drug: celecoxib  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the clinical efficacy of celecoxib vs placebo, in terms of inducing regression of oral leukoplakia lesions, in patients with hyperplastic or dysplastic oral leukoplakia.

Secondary

• Determine the effect of this drug in modulating multiple intermediate biomarkers (e.g., COX-2, PPARγ, or PPARδ) in normal and hyperplastic or dysplastic oral epithelia of these patients.
• Determine the safety of this drug in these patients.
• Determine the cost-effectiveness of this drug as a chemopreventative agent in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, cross-over study. Patients are stratified according to the pathology of the leukoplakia lesion (dysplasia vs hyperplasia). Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive oral celecoxib twice daily for 3 months.
• Arm II: Patients receive oral placebo twice daily for 3 months. All patients undergo biopsy. Patients then cross-over to the opposite treatment arm for 3 months.

In both arms, treatment continues in the absence of unacceptable toxicity or disease progression.

Patients are followed at 1 month.

PROJECTED ACCRUAL: A total of 27-60 patients (18-40 for study drug, 9-20 for placebo before cross-over) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of oral leukoplakia with hyperplasia or dysplasia
• Documented by baseline biopsy of oral lesions suspicious for leukoplakia
• For patients using dentures over the past 6 months, only lesions located on the ventral-lateral tongue or floor of the mouth are allowed
• No leukoplakia/hyperplasia secondary to mechanical irritation
• No carcinoma in situ of the oral cavity

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Not specified

Life expectancy

• At least 1 year

Hematopoietic

• Hemoglobin ≥ 10 g/dL (women) OR ≥ 11 g/dL (men)

Hepatic

• AST or ALT normal
• Bilirubin normal

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No myocardial infarction within the past 12 months
• No known active ischemic cardiac disease by stress test or echocardiogram

Gastrointestinal

• No history of gastrointestinal hemorrhage
• No known gastrointestinal ulcers within the past 2 years unless there is documentation of healed lesions by upper endoscopy
• No active or suspected peptic ulcer disease
• Negative stool guaiac test

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study treatment
• No use of snuff or chewing tobacco within the past 2 months
• No active invasive malignancy within the past 3 years except nonmelanoma skin cancer or in situ carcinomas
• No clinical evidence of chronic infectious disease
• No clinical evidence of connective tissue disease
• No known hypersensitivity (asthma, urticaria, or acute rhinitis induced by NSAIDs) to aspirin or other NSAIDs
• No known hypersensitivity to sulfonamides

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• At least 6 months since prior chronic or frequent use of systemic glucocorticoids
• No concurrent chronic or frequent use of systemic glucocorticoids

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior chronic or frequent (> 100 mg per day aspirin equivalent) use of nonsteroidal anti-inflammatory drugs (NSAIDs) for 7 of the past 14 days
• At least 3 months since prior experimental therapy
• No concurrent chronic or frequent use of NSAIDs
• Cardioprotective doses of aspirin ≤ 100 mg daily are allowed

Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States

Study chairs or principal investigators

Paul F. Engstrom, MD,  Principal Investigator,  Fox Chase Cancer Center   

Study ID Numbers:  CDR0000393574; FCCC-02028
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  January 7, 2005
ClinicalTrials.gov Identifier:  NCT00101335
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08