Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia

Sponsor

Barbara Ann Karmanos Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00056004

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer Lung Cancer	Drug: zileuton	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Phase II Trial Of Zileuton In Persons With Bronchial Dysplasia

Study Start Date :

Jun 1, 2003

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Mar 1, 2009

Outcome Measures

Primary Outcome Measures

Bronchial dysplasia number and grade at 6 months []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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