ACAPHA in Preventing Lung Cancer in Former Smokers With Bronchial 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.
Dietary Supplement: multi-herbal agent ACAPHA
Dietary Supplement: Sugar Pill
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia|
- Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- Changes in the severity of dysplasia by bronchial biopsy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Methylation biomarkers in the sputa, oral brush, and BAL cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Gene expression analysis of RNA from bronchial brush cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Volumetric measurement of CT scan-detected lung nodules before and after treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||September 2002|
|Study Completion Date:||November 2008|
|Primary Completion Date:||October 2008 (Final data collection date for primary outcome measure)|
|Active Comparator: ACAPHA||Dietary Supplement: multi-herbal agent ACAPHA|
|Placebo Comparator: Sugar Pill||Dietary Supplement: Sugar Pill|
- 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.
|Principal Investigator:||Stephen Lam, MD||British Columbia Cancer Agency|