ACAPHA in Preventing Lung Cancer in Former Smokers With Bronchial Intraepithelial Neoplasia
A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
- Determine the efficacy and safety of multi-herbal agent ACAPHA in former smokers with bronchial intraepithelial neoplasia.
- 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.
- 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.
- 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.
- 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 Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
- 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
- Atypical sputum cells as determined by computer-assisted image analysis
- 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)
- Exhaled carbon monoxide level < 5 ppm
- No invasive cancer on bronchoscopy or abnormal spiral chest CT scan suspicious of lung cancer
PATIENT CHARACTERISTICS:
- ECOG performance status 0 or 1
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Normal renal function tests (BUN, creatinine, urinalysis)
- Normal liver function tests (AST, ALT, bilirubin, alkaline phosphatase)
- No chronic active hepatitis or liver cirrhosis
- No acute bronchitis or pneumonia within the past month
- No known reaction to xylocaine
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:
- Acute or chronic respiratory failure
- Unstable angina
- Uncontrolled congestive heart failure
- Bleeding disorder
PRIOR CONCURRENT THERAPY:
- Not specified
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Sugar Pill
|
|
|
Active Comparator: ACAPHA
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions
Time Frame: 12 months
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Changes in the severity of dysplasia by bronchial biopsy
Time Frame: 6 months
|
6 months
|
|
Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL)
Time Frame: 12 months
|
12 months
|
|
MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies
Time Frame: 12 months
|
12 months
|
|
Methylation biomarkers in the sputa, oral brush, and BAL cells
Time Frame: 12 months
|
12 months
|
|
Gene expression analysis of RNA from bronchial brush cells
Time Frame: 12 months
|
12 months
|
|
Volumetric measurement of CT scan-detected lung nodules before and after treatment
Time Frame: 12 months
|
12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Stephen Lam, MD, British Columbia Cancer Agency
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CDR0000562055
- U01CA096109 (U.S. NIH Grant/Contract)
- BCCA-H02-61177-A002
- BCCA-R02-1177
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