RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Celecoxib and/or EKB-569 may be effective in preventing the development of oral cancer in patients who have oral leukoplakia.

PURPOSE: This randomized clinical trial is studying celecoxib and EKB-569 to see how well they work compared to celecoxib or EKB-569 alone in preventing oral cancer in patients with oral leukoplakia.

Condition	Treatment or Intervention
lip and oral cavity cancer Salivary Gland Cancer Precancerous Condition	Drug: EKB-569  Drug: celecoxib  Procedure: biological response modifier therapy  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: enzyme inhibitor therapy  Procedure: prostaglandin inhibition  Procedure: protein tyrosine kinase inhibitor therapy

Further Study Details: 

OBJECTIVES: Primary

• Compare the incidence of oral cancer in patients with aneuploid premalignant lesions in the oral cavity treated with celecoxib and EKB-569 vs celecoxib alone vs EKB-569 alone vs placebo.

Secondary

• Correlate the size, number, and appearance of oral premalignant lesions with cancer risk in patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Correlate molecular markers with oral cancer development in patients treated with these regimens.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to Nordic country of participation and cardioprotective acetylsalicylic acid use (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral celecoxib twice daily and oral placebo once daily.
• Arm II: Patients receive oral EKB-569 once daily and oral placebo twice daily.
• Arm III: Patients receive oral celecoxib twice daily and oral EKB-569 once daily.
• Arm IV: Patients receive one oral placebo twice daily and another oral placebo once daily. In all arms, treatment continues for 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed at every 3 months for 2 years and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 360 patients (90 per treatment arm) will be accrued for this study within 2-3 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of oral aneuploid premalignant lesion within the past 3 months
• Dysplastic white or red patches in the oral cavity with DNA aneuploidy determined by high resolving image cytometry
• Must have sufficient lesion to biopsy
• No prior or active head and neck cancer or lung cancer
• No known metastases to the head and neck area from other tumors

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1 OR
• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC > 3,000/mm^3
• Platelet count > 125,000/mm^3
• Hemoglobin normal

Hepatic

• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 1.5 times ULN
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN
• Calcium normal
• Glucose normal
• Phosphate normal
• Urea normal
• Uric acid normal

Cardiovascular

• No active coronary artery disease
• No unstable angina
• No uncontrolled hypertension
• No myocardial infarction within the past 6 months
• No congestive heart failure within the past 6 months
• No cardiac arrhythmia requiring antiarrhythmic therapy

Pulmonary

• No asthma
• No active chronic obstructive pulmonary disease
• No other moderate to severe respiratory illness within the past 6 months

Gastrointestinal

• No history of gastrointestinal bleeding or perforation
• No peptic ulcer disease without bleeding

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hypersensitivity to NSAIDs, sulfonamides, or cyclo-oxygenase-2 inhibitors
• No medical or psychological condition or other reason that would preclude study participation
• Sodium normal
• Potassium normal
• Magnesium normal
• CO_2 content normal
• Chloride normal
• No other cancer within the past 2 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• No concurrent adrenocorticosteroids

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 3 months since prior participation in any other experimental therapy study
• More than 14 days since prior routine non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin > 100 mg/day
• No concurrent fluconazole, lithium, warfarin, or NSAIDs
• Concurrent aspirin ≤ 100 mg/day allowed

Study chairs or principal investigators

Scott Michael Lippman, MD, FACP,  Principal Investigator,  M.D. Anderson Cancer Center   
Jon Sudbo, MD, PhD, DDS,  Principal Investigator,  Norwegian Radium Hospital   

Study ID Numbers:  CDR0000377364; MDA-2003-0824; MDA-NRH-2003-16; NCT00088842
Record last reviewed:  January 2005
Last Updated:  March 21, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088842
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08