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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

Primary Purpose

Lung Cancer, Precancerous Condition

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

budesonide/formoterol fumarate dihydrate inhalation aerosol

DNA methylation analysis

comparative genomic hybridization

microarray analysis

bronchoalveolar lavage

immunoenzyme technique

laboratory biomarker analysis

bronchoscopy

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring non-small cell lung cancer, precancerous condition

Eligibility Criteria

45 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

British Columbia Cancer Agency - Vancouver Cancer Centre

Outcomes

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)

Determination of DNA alterations in bronchial cells

Correlation of molecular features (e.g., methylation or gene expression changes) with biological features

Secondary Outcome Measures

Full Information

NCT ID

NCT00569712

First Posted

December 6, 2007

Last Updated

March 7, 2012

Sponsor

British Columbia Cancer Agency

Collaborators

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT00569712

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

British Columbia Cancer Agency

Collaborators

AstraZeneca

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer, Precancerous Condition

Keywords

non-small cell lung cancer, precancerous condition

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

budesonide/formoterol fumarate dihydrate inhalation aerosol

Intervention Type

Genetic

Intervention Name(s)

DNA methylation analysis

Intervention Type

Genetic

Intervention Name(s)

comparative genomic hybridization

Intervention Type

Genetic

Intervention Name(s)

microarray analysis

Intervention Type

Other

Intervention Name(s)

bronchoalveolar lavage

Intervention Type

Other

Intervention Name(s)

immunoenzyme technique

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Type

Procedure

Intervention Name(s)

bronchoscopy

Primary Outcome Measure Information:

Title

Time Frame

24 months

Title

Determination of DNA alterations in bronchial cells

Time Frame

24 months

Title

Correlation of molecular features (e.g., methylation or gene expression changes) with biological features

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

74 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen Lam, MD

Organizational Affiliation

British Columbia Cancer Agency

Official's Role

Principal Investigator

Facility Information:

Facility Name

British Columbia Cancer Agency - Vancouver Cancer Centre

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 4E6

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

24386300

Citation

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.

Results Reference

derived

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