Defined Green Tea Catechin Extract in Treating Women With Hormone Receptor Negative Stage I-III Breast Cancer

Phase 1

Completed

• Conditions: Progesterone Receptor-negative Breast Cancer; Stage I Breast Cancer; Stage IIIB Breast Cancer; Estrogen Receptor-negative Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer
• Interventions: Other: placebo; Other: quality-of-life assessment; Procedure: questionnaire administration; Drug: defined green tea catechin extract; Procedure: laboratory biomarker analysis

• Registration Number: NCT00516243
• Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Study Timeline

• Study Start: 2007-07
• Study First Submitted: 2007-08-14
• Study First Submitted QC: 2007-08-14
• Study First Posted: 2007-08-15
• Primary Completion: 2010-03
• Study Completion: 2010-03
• Status Verified: 2014-04
• Last Update Submitted: 2014-09-11
• Last Update Posted: 2014-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	placebo	Patients receive placebo PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm II (placebo)	quality-of-life assessment	Patients receive placebo PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm I (defined green tea catechin extract)	questionnaire administration	Patients receive defined green tea catechin extract PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm I (defined green tea catechin extract)	defined green tea catechin extract	Patients receive defined green tea catechin extract PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm II (placebo)	laboratory biomarker analysis	Patients receive placebo PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm I (defined green tea catechin extract)	quality-of-life assessment	Patients receive defined green tea catechin extract PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm I (defined green tea catechin extract)	laboratory biomarker analysis	Patients receive defined green tea catechin extract PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Arm II (placebo)	questionnaire administration	Patients receive placebo PO BID for 6 months in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
MTD defined as the dose that causes 25% DLT assessed using NCI CTCAE version 3.0	6 months

Secondary Outcome Measures

Name	Time	Method
Quantitative mammographic breast density	Up to 6 months	Generalized linear models will be used.
COMT genotype	Up to 6 months	Generalized linear models will be used.
Quality-of-life measures assessed using SF-36	Up to 6 months	Generalized linear models will be used.
Protein expression levels in benign breast tissue (Ki-67, p53, EGFR, HER2/neu, cleaved caspase-3, and ER)	Up to 6 months	Generalized linear models will be used.
Serum CRP levels	Up to 6 months	Generalized linear models will be used.
Breast tissue histology (nonproliferative, proliferative without atypia, atypical hyperplasia)	Up to 6 months	Generalized linear models will be used.
Eicosanoid levels (urine PGE-M)	Up to 6 months	Generalized linear models will be used.
Levels of oxidative damage biomarkers (urine 8-OHdG, isoprostane)	Up to 6 months	Generalized linear models will be used.
Hormone metabolite levels (estradiol, testosterone, IGF-1, IGFBP-3, SHBG)	Up to 6 months	Generalized linear models will be used.

Trial Locations

Locations (4)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States