Phase IIB Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer
Phase IIB Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer
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.
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.
ARM I: Patients receive oral genistein once daily.
ARM II: Patients receive oral placebo once daily.
In both arms, treatment continues for up to 6 months in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed at 30-37 days.
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:
Estimated 5-year risk of developing breast cancer using the Claus model:
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:
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