Phase IIB Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 126
- Locations
- 1
- Primary Endpoint
- Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling
Study Overview
Brief Summary
This randomized phase II trial is studying how well genistein works in preventing breast cancer in women at high risk for breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of genistein may prevent breast cancer in women at high risk for breast cancer.
Detailed Description
PRIMARY OBJECTIVE:
I. Determine the effect of genistein on the proliferation of breast epithelial cells obtained by fine needle aspiration (FNA), as measured by Ki-67 labeling index, in women who are at high risk for breast cancer.
SECONDARY OBJECTIVE:
I. Determine the effect of this drug on cellular and molecular parameters using epithelial cells obtained by FNA, nipple aspirate fluid, and blood from these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to menopausal status (premenopausal vs postmenopausal) and history of breast cancer (no history of breast cancer vs history of estrogen receptor [ER] positive breast cancer vs history of ER negative breast cancer). Patients are randomized to 1 of 2 treatment arms.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 25 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •No known soy intolerance
- •At increased risk of developing breast cancer in >= 1 previously unaffected breast, as defined by any of the following:
- •Estimated 5-year risk of developing breast cancer using the Gail model, as defined by 1 of the following:
- •Gail score >= 1.66%
- •Gail score >= 0.1% for women age 20-29 years
- •Gail score >= 1.0% for women age 30-39 years
- •Estimated 5-year risk of developing breast cancer using the Claus model:
- •Claus score >= 1.66%
- •Claus score >= 0.1% for women age 20-29 years
- •Claus score >= 1.0% for women age 30-39 years
- •Prior diagnosis of unilateral in situ or invasive breast cancer OR history of atypical hyperplasia, BRCA 1 and/or BRCA 2 positivity
- •History of lobular carcinoma in situ
- •No evidence of breast cancer, as determined by a negative mammogram within the past 6 months and a history and physical
- •No previously diagnosed breast cancer unless all systemic therapy (including endocrine therapy) was completed at least 1 year ago
- •Pre- or postmenopausal
- •ECOG performance status 0-1
- •Hemoglobin > 10.0 g/dL
- •Platelet count > 100,000/mm^3
- •Absolute neutrophil count > 1,000/mm^3
- •Creatinine < 2.0 mg/dL
- •SGPT < 82 U/L
- •SGOT < 68 U/L
- •Bilirubin < 3 mg/dL* [Note: * Patients with a higher level of bilirubin due to a familial metabolism may be eligible at the discretion of the investigator]
- •Life expectancy > 2 years
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception
- •Must be willing to keep a dietary diary
- •No venous thrombosis within the past year
- •No unrecognized or poorly controlled thyroid disease
- •No other cancer within the past 5 years except nonmelanomatous skin cancer or noninvasive cervical cancer
- •No other medical condition that, in the opinion of the investigator, would jeopardize either the patient or the integrity of the data obtained
- •None of the following for >= 2 weeks before the first random fine needle aspiration and during study participation:
- •Oral contraceptives
- •Soy supplements
- •High soy-containing foods
- •Fish oil supplements
- •Multivitamins
- •Vitamins C and E
- •Daily aspirin or nonsteroidal
- •Anti-inflammatory drugs
- •No other concurrent investigational agents
- •No concurrent warfarin or other blood thinners
- •Female patient
Exclusion Criteria
- •Women previously diagnosed with breast cancer will not be eligible unless all systemic therapy (including endocrine therapy) was completed at least one year previously
- •Currently pregnant, or planning to become pregnant during the study period
- •History of venous thrombosis within past year
- •Medical conditions, which, in the opinion of the investigators would jeopardize either the patient or the integrity of the data obtained
- •History of other cancer within the past five years, excluding non-melanomatous skin cancer, and non-invasive cervical cancer
- •Known soy intolerance
- •Unrecognized or uncontrolled thyroid disease, subjects may be on synthroid, but thyroid function must be in normal range or the patient's physician must document that the patient's thyroid is controlled.
- •Currently receiving any other investigational agents
- •Currently on coumadin, or other blood thinners
- •History of breast augmentation implants.
- •Rusults from patients who have <4000 epithelial cells in either the first or the second random Fine-needle aspiration (rFNA) will not be included in the study.
Arms & Interventions
Arm I (genistein)
Patients receive oral genistein once daily for up to 6 months.
Intervention: genistein (Drug)
Arm I (genistein)
Patients receive oral genistein once daily for up to 6 months.
Intervention: laboratory biomarker analysis (Other)
Arm II (placebo)
Patients receive oral placebo once daily for up to 6 months.
Intervention: placebo (Drug)
Outcomes
Primary Outcomes
Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling
Time Frame: 6 months - baseline
Breast epithelial tissue samples are used to measure the expression of the cell proliferation marker Ki-67, by counting the percentage of positive MIB-1 immunostained cells, denoted the Ki-67 labeling index. Mean change in the Ki-67 labeling index is assessed from baseline to 6 month follow up.
Secondary Outcomes
- Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells.(6 months - baseline)
- Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol(6 months - baseline)
- Plasma Concentration of Sex Hormone Binding Globulin (SHBG)(6 months - baseline)
- Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)(6 months - baseline)
- Monitor Drug Delivery by Measuring Plasma Genistein by HPLC(6 months - baseline)
- Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D(6 months - baseline)
- Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2(6 month - baseline)