Phase IB randomized, double-blinded, placebo-controlled, dose-escalation study of polyphenon E in women with a history of hormone receptor-negative breast cancer.

Abstract

TPS142 Background: Priorities in breast cancer (BC) chemoprevention include developing agents effective against hormone receptor (HR)-negative BC and validating intermediate biomarkers which correlate with BC risk. Numerous epidemiologic and preclinical studies support the anti- cancer and chemopreventive effects of green tea in BC. The main polyphenol of green tea, epigallacatechin gallate (EGCG), is a potent antioxidant which acts on multiple stages of carcinogenesis. The central hypothesis of this proposal is that the green tea polyphenol mixture, polyphenon E (Poly E), has activity for the secondary prevention of HR-negative BC. The primary objective of this phase IB trial is to demonstrate the safety of using Poly E over a 6- month period in patients with a history of HR-negative BC. Secondary exploratory objectives are to investigate the dose-related biologic effects of Poly E on breast tissue, radiographic, and serum-based biomarkers. Methods: This trial is a phase IB, randomized, double-blind, placebo-controlled study of oral Poly E 400 mg, 600 mg, or 800 mg bid for 6 months in 40 women with a history of stage I-III HR-negative BC (minimum of 6 months since completing chemotherapy, radiation therapy, or surgery; age 21-65). To date 40 patients have been enrolled. The primary endpoint of this dose escalation study is to determine the maximum tolerated dose of Poly E in this patient population according to the time-to-event continual reassessment method. Safety is assessed by monitoring clinical and laboratory parameters monthly for the duration of the study. Patients undergo a random core biopsy and mammogram of the contralateral breast at baseline and 6 months and serial blood/urine collections every 2 months. Laboratory correlates include breast tissue-based biomarkers (Ki-67, cleaved caspase-3, ER, EGFR, p53), mammographic density, serum hormone metabolites (estradiol, testosterone, IGF-I, IGFBP-3, SHBG), inflammatory and oxidative stress biomarkers (serum CRP, urine PGE-M, 8-OHdG, isoprostane). This study tests the safety and potential efficacy of a novel BC chemopreventive agent and evaluates a new approach for testing these agents. No significant financial relationships to disclose.