Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of zileuton may be an effective way to prevent lung cancer in patients who have bronchial dysplasia. PURPOSE: Randomized phase II trial to study the effectiveness of zileuton in preventing lung cancer in patients who have bronchial dysplasia.

Detailed Description
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OBJECTIVES: Determine the efficacy of zileuton, in terms of number of sites and grade of dysplastic lesions in the bronchial epithelium, in patients with documented bronchial dysplasia. Correlate the regression of bronchial dysplasia (number and grade) and improvement in sputum cytology with the modulation of molecular biomarkers in patients treated with this drug. Determine the overall toxicity of this drug in these patients. Determine the 6-month natural history of bronchial dysplasia in patients who are randomized to receive treatment with a placebo. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to smoking status (current vs recently quit smoker), and prior cancer (none vs lung or head and neck). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral zileuton 4 times daily for 6 months in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral placebo 4 times daily for 6 months in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks. PROJECTED ACCRUAL: Approximately 134 patients will be accrued for this study.

Official Title
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Phase II Trial Of Zileuton In Persons With Bronchial Dysplasia

Conditions
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Head and Neck Cancer, Lung Cancer

Intervention / Treatment
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* Drug: zileuton


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: At high risk for dysplasia, defined by 1 of the following criteria: Current or former smokers who have smoked at least 30 pack-years Former smokers must be enrolled within 20 years of complete smoking cessation Patients with curatively treated stage I non-small cell lung cancer* Patients with curatively treated stage I or II squamous cell carcinoma of the head and neck (limited to oral cavity, pharynx, or larynx)* NOTE: *At least 12 months post-curative therapy Histologic confirmation of mild to severe bronchial dysplasia on bronchoscopic biopsy required Moderate or severe atypia on sputum cytology required before bronchoscopy (not required for patients with prior lung or head and neck cancer) No evidence of malignancy by chest x-ray PATIENT CHARACTERISTICS: Age 18 and over (for patients with prior lung or head and neck malignancy) 35 and over (for all other patients) Performance status SWOG 0-1 Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL No bleeding disorder Hepatic Bilirubin no greater than upper limit of normal (ULN) Liver enzymes no greater than ULN PT/PTT no greater than ULN No active or chronic liver disease (even if transaminases have normalized) Renal Creatinine no greater than ULN Cardiovascular No unstable angina No uncontrolled heart failure Pulmonary No significant asthma or chronic obstructive pulmonary disease requiring chronic or periodic (at least once per year) steroids for flares No acute or chronic respiratory failure Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Willing and able to undergo serial bronchoscopic examinations No ongoing alcohol use (i.e., at least 1 glass of wine, beer, or a mixed drink per day on a regular basis) No other medical condition that would preclude safety during study participation No other active or invasive malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No hypersensitivity to study drug or any of its inactive ingredients PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy More than 3 months since prior corticosteroids* No concurrent corticosteroids* No concurrent anticancer hormonal agents NOTE: *Systemic or inhaled, including chronic administration Radiotherapy No concurrent radiotherapy Surgery Not specified Other More than 3 months since prior lipoxygenase inhibitors* More than 3 months since prior investigational agents More than 3 months since prior nutritional supplements (except 1 daily multivitamin) No concurrent nutritional supplements (except 1 daily multivitamin) No other concurrent lipoxygenase inhibitors* No other concurrent investigational agents No concurrent warfarin, beta-blockers, or theophylline No other concurrent antineoplastic agents No concurrent or chronic daily use of non-steroidal anti-inflammatory agents (NSAIDS) (except cardioprotective doses of aspirin less than 100 mg/day) Periodic use of NSAIDS allowed Concurrent participation in a smoking cessation program (including use of bupropion or nicotine gum or patch) allowed NOTE: *Systemic or inhaled, including chronic administration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: zileuton|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchial dysplasia number and grade at 6 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers (Ki-67, Cyclin D1, bcl-2, bax, caspase-3) by immunohistochemistry at 6 and 12 months |  |  | 
| Biomarkers (5-HETE, LTB-4) by blood and BAL levels at 6 and 12 months |  |  | 
| Adverse events as measured by number and severity monthly |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, small cell lung cancer, stage I non-small cell lung cancer, stage I squamous cell carcinoma of the hypopharynx, stage I squamous cell carcinoma of the larynx, stage I squamous cell carcinoma of the lip and oral cavity, stage I squamous cell carcinoma of the nasopharynx, stage I squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the larynx, stage II squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the nasopharynx, stage II squamous cell carcinoma of the oropharynx