Defined Green Tea Catechin Extract in Treating Women With Hormone Receptor Negative Stage I-III Breast Cancer
Condition: Estrogen Receptor-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This randomized phase I trial studies the side effects and best dose of defined green tea
      catechin extract in treating women with hormone receptor-negative stage I-III breast cancer.
      Green tea extract contains ingredients that may prevent or slow the growth of breast cancer.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      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.

      SECONDARY OBJECTIVES:

      I. Determine the efficacy of Polyphenon E in modulating histologic changes (nonproliferative,
      proliferative without atypia, atypical hyperplasia) on core biopsy of the contralateral
      breast.

      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
      contralateral breast.

      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.
    

Intervention name(s): placebo; quality-of-life assessment; questionnaire administration; laboratory biomarker analysis; defined green tea catechin extract
Intervention type(s): Other; Other; Procedure; Procedure; Drug
Intervention description(s): Given PO; Ancillary studies; Ancillary studies; Correlative studies; Given PO
Other intervention name(s): PLCB; quality of life assessment; Polyphenon E
Intervention MeSH terms: Epigallocatechin gallate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment