Zileuton in Preventing Lung Cancer in Patients With Bronchial Dysplasia

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00056004
First received: March 6, 2003
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Head and Neck Cancer
Lung Cancer
Drug: zileuton
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Phase II Trial Of Zileuton In Persons With Bronchial Dysplasia

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Bronchial dysplasia number and grade at 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biomarkers (Ki-67, Cyclin D1, bcl-2, bax, caspase-3) by immunohistochemistry at 6 and 12 months [ Designated as safety issue: No ]
  • Biomarkers (5-HETE, LTB-4) by blood and BAL levels at 6 and 12 months [ Designated as safety issue: No ]
  • Adverse events as measured by number and severity monthly [ Designated as safety issue: Yes ]

Enrollment: 38
Study Start Date: June 2003
Study Completion Date: March 2009
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00056004

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Omer Kucuk, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00056004     History of Changes
Other Study ID Numbers: CDR0000271915, P30CA022453, WSU-D-2405, WSU-093201MP4F
Study First Received: March 6, 2003
Last Updated: April 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Barbara Ann Karmanos Cancer Institute:
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

Additional relevant MeSH terms:
Lung Neoplasms
Head and Neck Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Zileuton
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Lipoxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 29, 2014