Phase II Trial of Polyphenon E in Current and Former Smokers With Bronchial Dysplasia
- To evaluate the efficacy and safety of Polyphenon E, a defined green tea catechin
extract, in current or former smokers with bronchial dysplasia and increased
inflammatory load as measured by C-reactive protein.
- To evaluate the ability of Polyphenon E to modulate other surrogate endpoint biomarkers
of oxidation stress, inflammation, aberrant methylation, cell cycle regulation,
apoptosis, oncogene/tumor suppressor gene expression, as well as phase I and II enzyme
regulation in biological samples from these patients.
- To establish a library of optical coherent tomography (OCT) images of the bronchial
epithelium with corresponding histopathology, nuclear morphometry, and other biomarker
- To assess the potential of OCT as a non-biopsy method for evaluating chemoprevention
OUTLINE: This is a multicenter study. Patients are stratified by gender. Patients are
randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral Polyphenon E twice daily for 3 months in the absence of
disease progression or unacceptable toxicity.
- Arm II: Patients receive a placebo twice daily for 3 months in the absence of disease
progression or unacceptable toxicity.
Patients undergo standard white-light bronchoscopy and fluorescence bronchoscopy with
optical coherence tomography (OCT) at baseline and at 3 months. During these procedures,
patients are evaluated using the Onco-LIFE clinical device, which digitally records OCT
images of abnormal areas or areas suspicious for intraepithelial neoplasia or invasive
carcinoma. Once these areas have been localized, patients are biopsied under fluorescence
bronchoscopy guidance to obtain both dysplastic bronchial epithelial tissue and normal
bronchial mucosa. Biopsy specimens are examined by immunostaining for tissue-based
biomarkers (i.e., Ki-67, cleaved caspase-3, p53, and VEGF). Patients also undergo oral
brushing, bronchial brushing, and bronchoalveolar lavage at baseline and at 3 months to
obtain bronchial epithelial cells for differential gene expression and methylation biomarker
studies (e.g., cDNA microarray analysis, polymerase chain reaction, and northern blotting).
Cytokines and other molecular biomarkers (i.e., C-reactive protein, surfactant protein D,
oxidized glutathione, interleukin [IL]-6, IL-13, and macrophage inflammatory protein-1
levels) are measured in blood and bronchoalveolar lavage fluid samples by enzyme-linked
immunoassay. Plasma EGCG levels are assessed by high-performance liquid chromatography.
Urine cotinine levels and exhaled carbon monoxide levels are also assessed.
After completion of study therapy, patients are followed at 1 month.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Change in the severity of dysplasia (as defined by WHO criteria) in bronchial biopsy specimens as assessed at baseline and at 3 months
Stephen Lam, MD
British Columbia Cancer Agency
United States: Food and Drug Administration