A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia
- 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
- 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
OUTLINE: Patients are stratified according to gender. Patients are randomized to 1 of 2
- 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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions
Stephen Lam, MD
British Columbia Cancer Agency
United States: Federal Government