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Green Tea Extract in Treating Women With Hormone Receptor-Negative Stage I, Stage II, or Stage III Breast Cancer
This study is ongoing, but not recruiting participants.

First Received on August 14, 2007.   Last Updated on November 14, 2011   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by (Responsible Party): M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00516243
  Purpose

RATIONALE: Green tea extract contains ingredients that may prevent or slow the growth of breast cancer.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of green tea extract in treating women with hormone receptor-negative stage I, stage II, or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Dietary Supplement: Polyphenon E
Other: Placebo
Phase I

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Modulation of histologic changes in breast tissue (nonproliferative, proliferative, atypia) on core biopsy of the contralateral breast [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Modulation of immunohistochemical protein expression (Ki-67, p53, EGFR, HER2/neu, cleaved caspase-3, and estrogen receptor) in breast tissue on core biopsy of the contralateral breast [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Modulation of mammographic breast density of the contralateral breast [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Modulation of hormone metabolites (serum estradiol, testosterone, IGF-1, IGFBP-3, SHBG) [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Modulation of eicosanoid levels (urine PGE-M) [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Modulation of biomarkers of oxidative damage (urine 8-OHdG, isoprostane) [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Modulation of serum C-reactive protein levels [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Activity of green tea extract (Polyphenon E) in relation to COMT genotype [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
  • Quality of life as assessed by Short Form 36 and attitudes toward complementary and alternative medicine in women with a history of breast cancer receiving Polyphenon E [ Time Frame: 6 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: June 2007
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polyphenon E
Starting dose 2 x 200 mg (400 mg) capsules of Poly E, 2 times per day for 6 months.
Dietary Supplement: Polyphenon E
Starting dose green tea catechin extract "Poly E" 400 mg twice a day (BID) of EGCG (2x200 mg caps BID), second escalated dose 600 mg BID of EGCG (3x200 mg caps BID), and third escalated dose 800 mg BID of EGCG (4x200 mg).
Other Names:
  • Poly E
  • Epigallocatechin gallate
  • EGCG
Placebo Comparator: Placebo Other: Placebo
Starting placebo dose will be matching study Poly E (2, 3 or 4 capsules BID).

Detailed Description:

OBJECTIVES:

Primary

  • Demonstrate the safety of green tea catechin extract (Polyphenon E) in women with a history of hormone receptor-negative breast cancer.
  • Determine the maximum tolerated dose of Polyphenon E in women with a history of hormone receptor-negative breast cancer.

Secondary

  • Determine the efficacy of Polyphenon E in modulating histologic changes (nonproliferative, proliferative without atypia, atypical hyperplasia) on core biopsy of the contralateral breast.
  • 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.
  • Determine the efficacy of Polyphenon E in modulating mammographic breast density of the contralateral breast.
  • Determine the efficacy of Polyphenon E in modulating hormone metabolites (serum estradiol, testosterone, IGF-1, IGFBP-3, SHBG).
  • Determine the efficacy of Polyphenon E in modulating eicosanoid levels (urine PGE-M).
  • Determine the efficacy of Polyphenon E in modulating biomarkers of oxidative damage (urine 8-OHdG, isoprostane).
  • Determine the efficacy of Polyphenon E in modulating serum C-reactive protein.
  • Determine the activity of Polyphenon E in relation to COMT genotype.
  • Assess quality of life and attitudes toward complementary and alternative medicine in women with a history of breast cancer.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive 1 of 3 dosages of oral green tea extract (Polyphenon E) twice daily for 6 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive oral placebo twice daily 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.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. History of histologically-confirmed stage I, II, or III estrogen receptor (ER)-negative & progesterone receptor (PR)-negative breast carcinoma w/o evidence of disease at trial entry. Participants w/ a resected local recurrence are eligible. Less than 10% ER & PR expression is considered negative. Site study physicians will review histology & hormone receptor status from pathology reports (this will be recorded in the Inclusion Criteria CRF). A release of medical records will be obtained to document hx of breast cancer diagnosis, staging, & treatment (this will be captured on the Med Hx CRF).
  2. Minimum of 6 months since last chemotherapy, radiation therapy, and/or breast surgery and no evidence of recurrent disease.
  3. Age 21 to 65 years. (Breast cancer is extremely rare in women less than 21 years. The maximum age of 65 years was chosen due to the higher prevalence of hyperplasia and atypia on breast biopsies from young to middle-aged high risk women.) Both pre- and postmenopausal women will be included in this study. Postmenopausal status will be defined as the absence of menses for > 12 months or serum FSH > 20 mIU/ml.
  4. Negative pregnancy testing (by serum b-hCG) within 2 weeks of study entry and at month 3 during therapy for women of child-bearing potential. 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. Women will be allowed to be on oral contraceptives, provided they have not changed their dose of these medications for at least 6 months prior to study entry. If a participant does become pregnant while on study, she will be removed from the study.
  5. Normal mammogram on contralateral breast within the past 12 months, defined as no new suspicious calcifications or other abnormal findings warranting a breast biopsy.
  6. ECOG performance status < 2 (Karnofsky > 60%)
  7. Participants must have normal organ and marrow function as defined as: Leukocytes >/= 3,000/mL; Absolute neutrophil count >/= 1,500/mL; Platelets >/= 100,000/mL; Total bilirubin within normal institutional limits; AST (SGOT)/ALT (SGPT) </= institutional ULN; Serum creatinine within normal institutional limits
  8. Willingness to abstain from all tea consumption for 30 days prior to baseline evaluation and during the study intervention. Many tea products, including black, green, white, oolong, and pu-erh teas, contain varying amounts of polyphenols. As we believe EGCG (the major polyphenol in green tea) is the active ingredient in Poly E that will affect our biomarker endpoints, we would like to eliminate any use of tea product-based polyphenols by our participants during the 6-month study intervention.
  9. Willingness to limit total daily caffeine consumption to < or = to three 8 ounce cups per day for 30 days prior to baseline evaluation and during study intervention. Total daily caffeine consumption should not exceed 375 mg/day. Study subjects will be provided a list of permissible medications, beverages, and foods which contain caffeine (Appendix K). Poly E contains only minimal amounts of caffeine. However, doses of up to 1000 mg twice daily of Poly E in combination with dietary caffeine intake may increase the rate of caffeine-related toxicity.
  10. Willingness to comply with all study intervention and follow-up procedures.
  11. Ability to understand and willingness to sign a written informed consent document.
  12. Since breast cancer is exceedingly rare in men, only women will be included in this study. Members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

  1. History of histologically-confirmed bilateral breast cancer.
  2. Evidence of metastatic breast cancer.
  3. Prior radiation therapy or implant in the contralateral breast.
  4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Poly E, such as green tea food products or supplements containing EGCG.
  5. Participants may not be receiving any other investigational agents for 30 days prior to baseline evaluation and during the study intervention (which will be captured on the Concomitant Medications CRFs).
  6. Any tea food products, > 375 mg/day of caffeine, medications, herbs, vitamin and mineral supplements that contain tea compounds or caffeine should not be taken for 30 days prior to baseline evaluation and during the study intervention. A 30-day washout period will be required for interested participants consuming greater amounts. Participants will be encouraged to limit their use of NSAIDs and selective COX-2 inhibitors. For those who take these medications on a regular basis, we will suggest that they maintain a constant dose.
  7. Uncontrolled or significant co-morbid illness including, but not limited to, active or serious infection requiring IV antibiotics; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia; active GI bleeding; active liver disease, active malignancy except for squamous or basal cell ca. of the skin, carcinoma in situ, Stages Ia or Ib invasive squamous cell ca. of the cervix treated by surgery and/or radiation therapy, Stage Ia Grade I adenocarcinoma of the endometrium treated w/ surgery; patients receiving active chemo- or radiotherapy; or psychiatric illness that would limit study compliance.
  8. Participants may not be taking hormone replacement therapy, tamoxifen, or raloxifene (which will be captured on the Concomitant Medications CRFs).
  9. History of gastrointestinal bleeding including, but not limited to, diverticulosis, peptic ulcer disease, erosive gastritis, or varices.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00516243

Locations
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Therese B. Bevers, MD, BS M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00516243     History of Changes
Other Study ID Numbers: 2006-0521, MDA-MDA04-4-01, MDA-2006-0521, CPMC-IRB-AAAB7638, CDR0000557580
Study First Received: August 14, 2007
Last Updated: November 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012