Phase IIb Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase IIb Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00290758
• Other study ID #: NCI 04B3
• Secondary ID: NWU03-1-04NCI 04
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 9, 2006
• Last updated: May 20, 2010
• Start date: January 2006
• Est. completion date: May 2011

Study information

• Verified date: May 2010
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: 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.

PURPOSE: This randomized phase II trial is studying how well genistein works in preventing breast cancer in women at high risk for breast cancer.

Description:

OBJECTIVES:

Primary

• 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

• 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.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 126
• Est. completion date: May 2011
• Est. primary completion date: August 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 25 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• Female patient

• 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 known soy intolerance

• 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

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• 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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Dietary Supplement:
• genistein
Given orally

Other:
• placebo
Given orally

Locations

Country	Name	City	State
United States	Lynn Sage Comprehensive Breast Center at Northwestern Memorial Hospital	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine effect upon proliferation of breast epithelial cells obtained by fine needle aspiration (FNA)	Determine intervention related effect upon proliferation of breast epithelial cells, obtained by fine needle aspiration (FNA), as measured by Ki-67 labeling index at screening and at six months.	At screening and at six months	Yes
Secondary	Epithelial cells obtained by FNA	Epithelial cells obtained by FNA i. Induction of apoptosis, as measured by activated caspase-3 ii. Cellular differentiation, as measured by cytomorphology of epithelial cells by quantitative image analysis iii. Alterations in hormone and cytokine related signaling pathways, as measured by real-time RTPCR expression of ERa, ?Rß , PgR, TGFa, TGFß, IGF-1, pS2, Ki67	At screening and at six months	No
Secondary	Nipple aspirate fluid	Nipple aspirate fluid i. Effect upon hormonal environment: Estradiol, Estrone sulphate, and Progesterone, by radioimmunoassay ii. Effect upon hormone action: Cathepsin D, pS2, and EGF, by ELISA	At secondary screening and at six months	Yes
Secondary	Blood Testing	Blood Testing i. Monitor drug delivery, by measuring plasma genistein, by HPLC ii. Effect upon hormonal environment: Serum estradiol, sex hormone binding globulin (SHBG), and progesterone, by radioimmunoassay iii. Screen for intervention related effects upon cell signaling, by measuring changes in protein phosphotyrosine levels in peripheral blood mononuclear cells, by Western blot	At presreening; secondary screening (if less than 45 years with intact ovaries); at day one, at one month and six months	Yes