Celecoxib in Preventing Head and Neck Cancer in Patients With Oral Leukoplakia

A Phase IIb Cancer Prevention Trial of Celecoxib, a Selective COX-2 Inhibitor, in Oral Leukoplakia

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.

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.

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