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 - Full Text View

Sponsored by:	British Columbia Cancer Agency
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00569712

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
Lung Cancer Precancerous/Nonmalignant Condition	Drug: budesonide/formoterol fumarate dihydrate inhalation aerosol Procedure: DNA methylation analysis Procedure: bronchoalveolar lavage Procedure: bronchoscopy Procedure: comparative genomic hybridization Procedure: gene expression profiling Procedure: immunoenzyme technique Procedure: laboratory biomarker analysis

MedlinePlus related topics: Asthma COPD (Chronic Obstructive Pulmonary Disease) Cancer Lung Cancer

Drug Information available for: Formoterol Arformoterol Arformoterol Tartrate Formoterol fumarate Budesonide Symbicort

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

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) [ Designated as safety issue: No ]
Determination of DNA alterations in bronchial cells [ Designated as safety issue: No ]
Correlation of molecular features (e.g., methylation or gene expression changes) with biological features [ Designated as safety issue: No ]
Safety and feasibility [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	January 2007
Estimated Primary Completion Date:	March 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569712

Locations

Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre	Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Stephen Lam, MD 604-675-8089

Sponsors and Collaborators

British Columbia Cancer Agency

Investigators

Principal Investigator:

Stephen Lam, MD

British Columbia Cancer Agency

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000577434, BCCA-H06-00209, ZENECA-BCCA-H06-00209
Study First Received:	December 6, 2007
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00569712
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

non-small cell lung cancer
precancerous/nonmalignant condition

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Precancerous Conditions
Symbicort
Budesonide
Asthma
Lung Diseases, Obstructive

Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Formoterol
Carcinoma, Non-Small-Cell Lung
Pulmonary Disease, Chronic Obstructive

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Respiratory Tract Neoplasms
Respiratory System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic beta-Agonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents

Glucocorticoids
Hormones
Adrenergic Agonists
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Bronchodilator Agents

ClinicalTrials.gov processed this record on January 15, 2009