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Genistein in Preventing Breast Cancer in Women at High Risk for Breast Cancer

Primary Purpose

Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
placebo
genistein
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer

Eligibility Criteria

25 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Northwestern University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (genistein)

Arm II (placebo)

Arm Description

Patients receive oral genistein once daily for up to 6 months.

Patients receive oral placebo once daily for up to 6 months.

Outcomes

Primary Outcome Measures

Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling
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 Outcome Measures

Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)
Mean change in the concentration of EGF found in nipple aspirate fluid is assessed from baseline to 6 month follow up.
Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells.
Cytologic atypia evaluation was performed on Papanicolau stained Thin Prep slides using standard criteria, which were also used for spectral spatial imaging. Cell clusters were used to generate image stacks with the Nuance LCTF-based imaging system (CRI Inc). The image data was collected as percent pixels assigned as "atypical". Mean change in the percent pixels assigned "atypical" is assessed from baseline to 6 month follow up.
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol
Mean change in concentration of estradiol measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Monitor Drug Delivery by Measuring Plasma Genistein by HPLC
Drug delivery is measured be concentration of genistein in plasma using High Performance Liquid Chromatography (HPLC). Mean change in concentration of plasma genistein is assessed from baseline to 6 month follow up.
Plasma Concentration of Sex Hormone Binding Globulin (SHBG)
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D
Mean change in concentration of Cathepsin D measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2
Mean change in concentration of protein ps2 measured in nipple aspiration fluid assessed from baseline to 6 month follow up.

Full Information

First Posted
February 9, 2006
Last Updated
December 14, 2016
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00290758
Brief Title
Genistein in Preventing Breast Cancer in Women at High Risk for Breast Cancer
Official Title
Phase IIB Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
126 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (genistein)
Arm Type
Experimental
Arm Description
Patients receive oral genistein once daily for up to 6 months.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive oral placebo once daily for up to 6 months.
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
genistein
Other Intervention Name(s)
CI 75610, genisteol, genisterin, prunetol, sophoricol
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Change in Breast Epithelial Cell Proliferation as Measured by Ki-67 Labeling
Description
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.
Time Frame
6 months - baseline
Secondary Outcome Measure Information:
Title
Measurement of Change in Concentration of Epidermal Growth Factor (EGF) Found in Nipple Aspirate Fluid (NAF)
Description
Mean change in the concentration of EGF found in nipple aspirate fluid is assessed from baseline to 6 month follow up.
Time Frame
6 months - baseline
Title
Change in Cytomorphologic Assessment of Atypia and Spectral Imaging Analysis of Atypica Features in Epithelial Cells.
Description
Cytologic atypia evaluation was performed on Papanicolau stained Thin Prep slides using standard criteria, which were also used for spectral spatial imaging. Cell clusters were used to generate image stacks with the Nuance LCTF-based imaging system (CRI Inc). The image data was collected as percent pixels assigned as "atypical". Mean change in the percent pixels assigned "atypical" is assessed from baseline to 6 month follow up.
Time Frame
6 months - baseline
Title
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Estradiol
Description
Mean change in concentration of estradiol measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Time Frame
6 months - baseline
Title
Monitor Drug Delivery by Measuring Plasma Genistein by HPLC
Description
Drug delivery is measured be concentration of genistein in plasma using High Performance Liquid Chromatography (HPLC). Mean change in concentration of plasma genistein is assessed from baseline to 6 month follow up.
Time Frame
6 months - baseline
Title
Plasma Concentration of Sex Hormone Binding Globulin (SHBG)
Time Frame
6 months - baseline
Title
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): Cathepsin D
Description
Mean change in concentration of Cathepsin D measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Time Frame
6 months - baseline
Title
Breast Endocrine Environment Measured in Nipple Aspiration Fluid (NAF): ps2
Description
Mean change in concentration of protein ps2 measured in nipple aspiration fluid assessed from baseline to 6 month follow up.
Time Frame
6 month - baseline

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seema Khan
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
22307566
Citation
Khan SA, Chatterton RT, Michel N, Bryk M, Lee O, Ivancic D, Heinz R, Zalles CM, Helenowski IB, Jovanovic BD, Franke AA, Bosland MC, Wang J, Hansen NM, Bethke KP, Dew A, Coomes M, Bergan RC. Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial. Cancer Prev Res (Phila). 2012 Feb;5(2):309-19. doi: 10.1158/1940-6207.CAPR-11-0251.
Results Reference
derived

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Genistein in Preventing Breast Cancer in Women at High Risk for Breast Cancer

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