Studying Genes in Blood and Lung Fluid Samples From Patients With Chronic Obstructive Pulmonary Disease With or Without a Previous Diagnosis of Lung Cancer or With Asthma Treated With Budesonide and Formoterol

A Pilot Comparative Study of the Genomic Molecular and Clinical Profiles of Patients With Lung Cancer, COPD, or Asthma Treated With Symbicort Turbuhaler

RATIONALE: Studying the genes expressed in samples of blood and lung fluid in the laboratory from patients receiving budesonide and formoterol may help doctors learn more about the effect of budesonide and formoterol on gene expression and biomarkers.

PURPOSE: This clinical trial is studying genes in blood and lung fluid samples from patients with chronic obstructive pulmonary disease, with or without a previous diagnosis of lung cancer, or with asthma treated with budesonide and formoterol.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Precancerous Condition
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: immunoenzyme technique; Genetic: DNA methylation analysis; Procedure: bronchoscopy; Genetic: comparative genomic hybridization; Genetic: microarray analysis; Drug: budesonide/formoterol fumarate dihydrate inhalation aerosol; Other: bronchoalveolar lavage

Detailed Description

OBJECTIVES:

• To collect and integrate background information on the genetic, epigenetic, and gene expression profiles of small airway cells and markers of inflammation in bronchoalveolar lavage fluid and blood from patients with chronic obstructive pulmonary disease (COPD) with or without a prior diagnosis of lung cancer and from patients with asthma.
• To examine the effects of budesonide/formoterol fumarate dihydrate inhalation aerosol (Symbicort Turbuhaler) on methylation and gene expression profiles of airway cells as well as on inflammatory, oxidant, and other pathways in these patients.
• To determine if it would be feasible to conduct a larger study that would allow a definitive analysis of the differences in the bronchial cells and the inflammatory proteins in bronchial secretions and blood from patients with COPD with or without a prior diagnosis of lung cancer.

OUTLINE: Patients receive budesonide/formoterol fumarate dihydrate inhalation aerosol (Symbicort Turbuhaler) twice daily for 4 weeks in the absence of disease progression or unacceptable toxicities.

Patients undergo blood sample collection and bronchoscopy at baseline and at 4 weeks. Blood and bronchoalveolar fluid samples are analyzed for inflammatory biomarker measurements. Bronchial brushing cell samples are analyzed by comparative genomic hybridization array, whole genome methylation array, and gene expression profiling.

After completion of study treatment, patients are followed at 1 week by telephone interview.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • Former smoker with a 30 pack-year smoking history and mild to moderate degree of airflow obstruction, meeting the following criterion:

    • GOLD class 1 or 2 chronic obstructive pulmonary disease (COPD), defined as a post-bronchodilator FEV_1 < 80% of predicted and FEV_1 to FVC ratio < 70%
  • Former smoker with COPD and has undergone a prior curative resection for stage 0 or I non-small cell lung cancer

  • Non-smoker with mild to moderate bronchial asthma not already on inhaled corticosteroids, meeting the following criterion:

    • Fully reversible airflow obstruction and post-bronchodilator FEV_1 > 80% of predicted
• No invasive cancer on bronchoscopy or abnormal spiral chest CT scan suspicious of lung cancer

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Willing to use study drug twice daily regularly
• Willing to undergo a bronchoscopy
• Not planning to donate blood during study participation
• No known or suspected hypersensitivity to budesonide, formoterol fumarate dihydrate, or excipients in study drug
• No known reaction to xylocaine
• No history of allergy to Symbicort, Pulmicort, or Oxeze Turbuhaler
• No significant medical condition, such as acute or chronic respiratory failure, unstable angina, uncontrolled congestive heart failure, or bleeding disorder that, in the opinion of the investigator, may either put the patient at risk due to study participation or preclude the patient's ability to complete the study
• No travel or planned hospitalization that would preclude the patient's ability to complete the study

PRIOR CONCURRENT THERAPY:

• More than 6 months since prior and no other concurrent inhaled corticosteroids (e.g., budesonide [Pulmicort Turbuhaler], fluticasone [Flovent], beclomethasone dipropionate [QVAR], or fluticasone/salmeterol [Advair])
• More than 6 months since prior and no concurrent oral steroids (e.g., prednisone)
• No concurrent montelukast
• No concurrent immunomodulatory or immunosuppressive medication (e.g., anti-TNF or methotrexate)
• No concurrent beta-adrenergic blockers (e.g., atenolol or inderal), orally or as eye drops

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in the concentrations of cytokines in plasma and bronchoalveolar lavage fluid as well as gene expression profiles before and after treatment with budesonide/formoterol fumarate dihydrate inhalation aerosol (Symbicort Turbuhaler)	24 months
Determination of DNA alterations in bronchial cells	24 months
Correlation of molecular features (e.g., methylation or gene expression changes) with biological features	24 months

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Stephen Lam, MD, British Columbia Cancer Agency

Publications and helpful links

General Publications

• Um SJ, Lam S, Coxson H, Man SF, Sin DD. Budesonide/formoterol enhances the expression of pro Surfactant Protein-B in lungs of COPD patients. PLoS One. 2013 Dec 26;8(12):e83881. doi: 10.1371/journal.pone.0083881. eCollection 2013.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 6, 2007
• First Submitted That Met QC Criteria: December 6, 2007
• First Posted (Estimate): December 7, 2007

Study Record Updates

• Last Update Posted (Estimate): March 9, 2012
• Last Update Submitted That Met QC Criteria: March 7, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; precancerous condition
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Precancerous Conditions; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Chelating Agents; Sequestering Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate; Dimercaprol
• Other Study ID Numbers: CDR0000577434; BCCA-H06-00209; ZENECA-BCCA-H06-00209