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Study Summary
No. 2006-0521:.......Breast......Therese B. Bevers......Clinical Cancer Prevention
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Study Summary Title
Study Summary
Number:
2006-0521
Study Title:Phase 1b Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Women with a History of Hormone Receptor-Negative Breast Cancer
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Physician New Patient Referral
Name:Therese B. BeversPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Clinical Cancer PreventionReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-745-8048
Contact us about clinical trials
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General Information
Disease Group:BreastSupported By:N/A
Phase of Study:Phase IReturn
Visit:
8 visits during study
Treatment
Agents:
Polyphenon EHome Care:Not applicable
Treatment Loc:Independent Multicenter Arrangements
Estimated
Length of Stay
in Houston:
Not applicable
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of the Polyphenon E (Poly E) that can be given to patients who have had hormone
receptor-negative breast cancer. Another goal is to test the safety of Poly E
at different dose levels.
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Study Objectives / Outcomes
1.1. The primary objectives of this study are to 1) demonstrate the safety and 2) determine the maximum tolerated dose (MTD) of Polyphenon E (Poly E) contained in up to 800 mg EGCG bid given over a six-month period in women with a history of hormone receptor-negative breast cancer.

1.2. The secondary objectives of this study are to investigate the dose-related biologic effects of Poly E in this population (in order of decreasing priority):
    1.2.1. Determine the efficacy of Poly E in modulating histologic changes (nonproliferative, proliferative without atypia, atypical hyperplasia) on core biopsy of the contralateral breast.
    1.2.2. Determine the efficacy of Poly 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.
    1.2.3. Determine the efficacy of Poly E in modulating mammographic breast density of the contralateral breast.
    1.2.4. Determine the efficacy of Poly E in modulating hormone metabolites (serum estradiol, testosterone, IGF-1, IGFBP-3, SHBG).
    1.2.5. Determine the efficacy of Poly E in modulating eicosanoid levels (urine PGE-M).
    1.2.6. Determine the efficacy of Poly E in modulating biomarkers of oxidative damage (urine 8-OHdG, isoprostane).
    1.2.7. Determine the efficacy of Poly E in modulating serum C-reactive protein.
    1.2.8. Determine Poly E activity in relation to COMT genotype.
    1.2.9. Assess quality of life (QOL) as measured by the Short Form-36 (SF-36) and attitudes toward complementary and alternative medicine (CAM) in women with a history of breast cancer.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:03/09/2007
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:40
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

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 eligibile. 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 wks. 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 shoud 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; pts. 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.

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Links
Registration Number: NCT00516243
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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