Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women With a History of Hormone Receptor-Negative Breast Cancer
I. Demonstrate the safety of green tea catechin extract (Polyphenon E) in women with a
history of hormone receptor-negative breast cancer.
II. Determine the maximum tolerated dose of Polyphenon E in women with a history of hormone
receptor-negative breast cancer.
I. Determine the efficacy of Polyphenon E in modulating histologic changes
(nonproliferative, proliferative without atypia, atypical hyperplasia) on core biopsy of the
II. Determine the efficacy of Polyphenon E in modulating immunohistochemical expression of
Ki-67 (proliferation index), p53, EGFR, HER2/neu, cleaved caspase-3 (apoptosis marker), and
estrogen receptor on core biopsy tissue of the contralateral breast.
III. Determine the efficacy of Polyphenon E in modulating mammographic breast density of the
IV. Determine the efficacy of Polyphenon E in modulating hormone metabolites (serum
estradiol, testosterone, IGF-1, IGFBP-3, SHBG).
V. Determine the efficacy of Polyphenon E in modulating eicosanoid levels (urine PGE-M).
VI. Determine the efficacy of Polyphenon E in modulating biomarkers of oxidative damage
(urine 8-OHdG, isoprostane).
VII. Determine the efficacy of Polyphenon E in modulating serum C-reactive protein.
VIII. Determine the activity of Polyphenon E in relation to COMT genotype. IX. Assess
quality of life and attitudes toward complementary and alternative medicine in women with a
history of breast cancer.
OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive defined green tea catechin extract orally (PO) twice daily (BID) for
6 months in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo PO BID for 6 months in the absence of disease progression
or unacceptable toxicity.
Patients undergo a core biopsy and mammogram of the contralateral breast at baseline and
after 6 months for histological evaluation, IHC analysis, and mammographic density reading.
Core biopsy tissue is assessed for proliferative changes and presence of atypia using
standardized histological criteria. Core biopsy tissue is also analyzed by IHC for the
following proteins: Ki-67 (proliferation index), p53, EGFR, HER2/neu, cleaved caspase-3
(apoptosis marker), and estrogen receptor (ER). Blood and urine samples are collected at
baseline and every 2 months during treatment to measure drug effect biomarkers: serum
estradiol, testosterone, insulin-like growth factor-1 (IGF-1), IGF binding protein-3
(IGFBP-3), and sex hormone-binding globulin (SHBG) by immunological laboratory methods;
urine prostaglandin levels (PGE-M) by tandem mass spectrometry; urine oxidative damage
markers (8-OHdG, isoprostane) and serum C-reactive protein (CRP) by ELISA; and
catechol-O-methyltransferase (COMT) genotype (at baseline only).
Patients complete a questionnaire assessing quality of life (SF-36) and attitudes toward
complementary and alternative medicine at baseline and at 6 months.
After completion of study treatment, patients are followed for 1 month.
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
MTD defined as the dose that causes 25% DLT assessed using NCI CTCAE version 3.0
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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