Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia

April 25, 2013 updated by: Barbara Ann Karmanos Cancer Institute

Phase II Trial Of Zileuton In Persons With Bronchial Dysplasia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Bronchial dysplasia number and grade at 6 months

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2003

Primary Completion (Actual)

September 1, 2006

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

March 6, 2003

First Submitted That Met QC Criteria

March 6, 2003

First Posted (Estimate)

March 7, 2003

Study Record Updates

Last Update Posted (Estimate)

April 29, 2013

Last Update Submitted That Met QC Criteria

April 25, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000271915
  • P30CA022453 (U.S. NIH Grant/Contract)
  • WSU-D-2405
  • WSU-093201MP4F

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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