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Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia

Information source: Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Head and Neck Cancer; Lung Cancer

Intervention: zileuton (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Barbara Ann Karmanos Cancer Institute

Official(s) and/or principal investigator(s):
Omer Kucuk, MD, Study Chair, Affiliation: Barbara Ann Karmanos Cancer Institute


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.

Clinical Details

Official title: Phase II Trial Of Zileuton In Persons With Bronchial Dysplasia

Study design: Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Primary outcome: Bronchial dysplasia number and grade at 6 months

Secondary outcome:

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

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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.



- 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


- 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


- 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


- 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


- 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


- 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)


- Creatinine no greater than ULN


- No unstable angina

- No uncontrolled heart failure


- 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


- 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


- Not specified


- 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


- Not specified


- 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

Locations and Contacts

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2003
Last updated: April 25, 2013

Page last updated: August 23, 2015

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