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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

This study has been completed.
Sponsor:
Collaborator:
Astra Zeneca Canada
Information provided by (Responsible Party):
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT00569712
First received: December 6, 2007
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Precancerous Condition
Drug: budesonide/formoterol fumarate dihydrate inhalation aerosol
Genetic: DNA methylation analysis
Genetic: comparative genomic hybridization
Genetic: microarray analysis
Other: bronchoalveolar lavage
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Procedure: bronchoscopy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Comparative Study of the Genomic Molecular and Clinical Profiles of Patients With Lung Cancer, COPD, or Asthma Treated With Symbicort Turbuhaler

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • 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) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Determination of DNA alterations in bronchial cells [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Correlation of molecular features (e.g., methylation or gene expression changes) with biological features [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: January 2007
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   45 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00569712

Locations
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
British Columbia Cancer Agency
Astra Zeneca Canada
Investigators
Principal Investigator: Stephen Lam, MD British Columbia Cancer Agency
  More Information

Additional Information:
No publications provided by British Columbia Cancer Agency

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT00569712     History of Changes
Other Study ID Numbers: CDR0000577434, BCCA-H06-00209, ZENECA-BCCA-H06-00209
Study First Received: December 6, 2007
Last Updated: March 7, 2012
Health Authority: Canada: Ethics Review Committee

Keywords provided by British Columbia Cancer Agency:
non-small cell lung cancer
precancerous condition

Additional relevant MeSH terms:
Lung Diseases, Obstructive
Lung Neoplasms
Precancerous Conditions
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Budesonide
Formoterol
Symbicort
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents

ClinicalTrials.gov processed this record on November 25, 2014