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

Stage IIIA Breast Cancer Clinical Trial

Official title:

Phase IB Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women With a History of Hormone Receptor-Negative Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00516243
• Other study ID #: NCI-2009-00858
• Secondary ID: NCI-2009-00858IR
• Status: Completed
• Phase: Phase 1
• First received: August 14, 2007
• Last updated: September 11, 2014
• Start date: July 2007
• Est. completion date: March 2010

Study information

• Verified date: April 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years to 65 Years

Eligibility

Criteria:

• History of histologically confirmed stage I, II, or III breast carcinoma without evidence of disease at study entry

• No evidence of recurrent disease (patients with resected local recurrence are eligible)

• Normal mammogram of the contralateral breast within the past 12 months, defined as no new suspicious calcifications or other abnormal findings warranting a breast biopsy

• No history of histologically confirmed bilateral breast cancer

• No evidence of metastatic breast cancer

• Registered in the outpatient medical oncology clinic at Columbia University Medical Center (CUMC), MD Anderson Cancer Center (MDACC), Memorial Sloan Kettering Cancer Center (MSKCC), or the Weill-Cornell campus of New York Presbyterian Hospital (NYP-WC)

• Hormone receptor status: Estrogen- and progesterone-receptor negative

• Menopausal status: Pre- or postmenopausal

• ECOG performance status < 2 (Karnofsky > 60%)

• Leukocytes >= 3,000/uL

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin within normal institutional limits

• AST/ALT =< 2.5 times institutional upper limit of normal

• Serum creatinine within normal institutional limits

• Not pregnant or nursing

• Negative pregnancy test

• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to green tea extract (Polyphenon E), such as green tea food products or supplements containing EGCG

• No history of gastrointestinal bleeding including, but not limited to, any of the following: Diverticulosis; Peptic ulcer disease; Erosive gastritis; Varices

• No uncontrolled or significant co-morbid illness including, but not limited to, any of the following: active or serious infection requiring intravenous antibiotics; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; active gastrointestinal bleeding; active liver disease; psychiatric illness/social situations that would limit compliance with study requirements

• No active malignancy, except for squamous cell carcinoma of the skin; basal cell carcinoma of the skin; carcinoma in situ; stage IA or IB invasive squamous cell carcinoma of the cervix treated by surgery and/or radiation therapy; or stage IA grade 1 adenocarcinoma of the endometrium treated by surgery

• At least 6 months since prior chemotherapy, radiation therapy, and/or breast surgery

• No prior radiation therapy or implant in the contralateral breast

• More than 30 days since prior and no concurrent medications, herbs, or vitamin and mineral supplements that contain tea compounds or caffeine

• At least 30 days since prior and no other concurrent investigational agents

• At least 30 days since prior and no concurrent tea consumption

• Willing to limit regular coffee consumption to =< three 8-ounce cups per day for 30 days prior to baseline evaluation and during the study intervention

• Total daily caffeine consumption should not exceed 375 mg/day

• No concurrent hormone replacement therapy, tamoxifen, or raloxifene

• Concurrent oral contraceptives allowed provided the dose has not been changed for at least 6 months prior to study entry

• No concurrent chemotherapy or radiation therapy

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• 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

Intervention

Other:
• placebo
Given PO
• quality-of-life assessment
Ancillary studies

Procedure:
• questionnaire administration
Ancillary studies
• laboratory biomarker analysis
Correlative studies

Drug:
• defined green tea catechin extract
Given PO

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD defined as the dose that causes 25% DLT assessed using NCI CTCAE version 3.0		6 months	Yes
Secondary	Breast tissue histology (nonproliferative, proliferative without atypia, atypical hyperplasia)	Generalized linear models will be used.	Up to 6 months	No
Secondary	COMT genotype	Generalized linear models will be used.	Up to 6 months	No
Secondary	Quality-of-life measures assessed using SF-36	Generalized linear models will be used.	Up to 6 months	No
Secondary	Protein expression levels in benign breast tissue (Ki-67, p53, EGFR, HER2/neu, cleaved caspase-3, and ER)	Generalized linear models will be used.	Up to 6 months	No
Secondary	Quantitative mammographic breast density	Generalized linear models will be used.	Up to 6 months	No
Secondary	Hormone metabolite levels (estradiol, testosterone, IGF-1, IGFBP-3, SHBG)	Generalized linear models will be used.	Up to 6 months	No
Secondary	Eicosanoid levels (urine PGE-M)	Generalized linear models will be used.	Up to 6 months	No
Secondary	Levels of oxidative damage biomarkers (urine 8-OHdG, isoprostane)	Generalized linear models will be used.	Up to 6 months	No
Secondary	Serum CRP levels	Generalized linear models will be used.	Up to 6 months	No