ACAPHA in Preventing Lung Cancer in Former Smokers With Bronchial Intraepithelial Neoplasia
Study Details
Study Description
Brief Summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of ACAPHA, a combination of six herbs, may prevent lung cancer from forming in former smokers with bronchial intraepithelial neoplasia.
PURPOSE: This randomized phase II trial is studying the side effects and how well ACAPHA works in preventing lung cancer in former smokers with bronchial intraepithelial neoplasia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
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Determine the efficacy and safety of multi-herbal agent ACAPHA in former smokers with bronchial intraepithelial neoplasia.
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Evaluate whether ACAPHA can modulate other surrogate endpoint biomarkers of aberrant methylation, cell cycle regulation, apoptosis, as well as phase I and II enzyme regulation.
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Establish a library of in vivo confocal microendoscopy images with corresponding histopathology, nuclear morphometry, and other biomarker information to assess the potential of confocal microendoscopy as a nonbiopsy method in assessing the effect of chemoprevention agents.
OUTLINE: Patients are stratified according to gender. Patients are randomized to 1 of 2 arms.
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Arm I: Patients receive oral multi-herbal agent ACAPHA twice daily for 6 months. Patients achieving a partial response receive an additional 6 months of ACAPHA.
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Arm II: Patients receive oral placebo twice daily for 6 months. Patients achieving a partial response receive an additional 6 months of placebo. Patients with progressive disease receive ACAPHA twice daily for 6 months.
Patients undergo sputum cytology, oral and bronchial brushings, bronchoalveolar lavage, and bronchial tissue biopsies at baseline and at 6 and 12 months. Samples are analyzed for histopathological and morphometric cell changes; MIB-1 bcl-2, and TUNEL immunostaining; methylation biomarkers; and gene expression analysis of RNA.
After completion of study therapy, patients are followed at 1 and 6 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: ACAPHA
|
Dietary Supplement: multi-herbal agent ACAPHA
|
| Placebo Comparator: Sugar Pill
|
Dietary Supplement: Sugar Pill
|
Outcome Measures
Primary Outcome Measures
- Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions [12 months]
Secondary Outcome Measures
- Changes in the severity of dysplasia by bronchial biopsy [6 months]
- Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL) [12 months]
- MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies [12 months]
- Methylation biomarkers in the sputa, oral brush, and BAL cells [12 months]
- Gene expression analysis of RNA from bronchial brush cells [12 months]
- Volumetric measurement of CT scan-detected lung nodules before and after treatment [12 months]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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One or more areas of bronchial intraepithelial neoplasia (IEN) (metaplasia/dysplasia) with a nuclear morphometry index > 1.36 and a surface diameter > 1.2 mm on autofluorescence bronchoscopy
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Atypical sputum cells as determined by computer-assisted image analysis
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Former smoker (i.e., stopped smoking at least 1 year ago) who has smoked at least 30 pack-years (i.e., 1 pack/day for 30 years or more)
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Exhaled carbon monoxide level < 5 ppm
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No invasive cancer on bronchoscopy or abnormal spiral chest CT scan suspicious of lung cancer
PATIENT CHARACTERISTICS:
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ECOG performance status 0 or 1
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception
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Normal renal function tests (BUN, creatinine, urinalysis)
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Normal liver function tests (AST, ALT, bilirubin, alkaline phosphatase)
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No chronic active hepatitis or liver cirrhosis
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No acute bronchitis or pneumonia within the past month
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No known reaction to xylocaine
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No medical condition that, in the opinion of the investigator, could jeopardize the patient's safety during participation in the study, including any of the following:
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Acute or chronic respiratory failure
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Unstable angina
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Uncontrolled congestive heart failure
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Bleeding disorder
PRIOR CONCURRENT THERAPY:
- Not specified
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- British Columbia Cancer Agency
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Stephen Lam, MD, British Columbia Cancer Agency
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000562055
- U01CA096109
- BCCA-H02-61177-A002
- BCCA-R02-1177