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

Sponsor:	Northwestern University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00290758

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Dietary Supplement: genistein Other: placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	Phase IIb Trial of G-2535 (Unconjugated Isoflavones-100) in Women at High Risk for Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Genistein

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

Determine effect upon proliferation of breast epithelial cells obtained by fine needle aspiration (FNA) [ Time Frame: At screening and at six months ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Epithelial cells obtained by FNA [ Time Frame: At screening and at six months ] [ Designated as safety issue: No ]
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 ERα, ΕRβ , PgR, TGFα, TGFβ, IGF-1, pS2, Ki67
Nipple aspirate fluid [ Time Frame: At secondary screening and at six months ] [ Designated as safety issue: Yes ]
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
Blood Testing [ Time Frame: At presreening; secondary screening (if less than 45 years with intact ovaries); at day one, at one month and six months ] [ Designated as safety issue: Yes ]
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

Enrollment:	126
Study Start Date:	January 2006
Estimated Study Completion Date:	May 2011
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive oral genistein once daily for up to 6 months.	Dietary Supplement: genistein Given orally
Placebo Comparator: Arm II Patients receive oral placebo once daily for up to 6 months.	Other: placebo Given orally

Detailed 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.

Eligibility

Ages Eligible for Study:	25 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290758

Locations

United States, Illinois
Lynn Sage Comprehensive Breast Center at Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Northwestern University
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

National Cancer Institute (NCI)

Investigators

Study Chair:

Seema A. Khan, MD

Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Seema Khan, MD, Northwestern University
ClinicalTrials.gov Identifier:	NCT00290758 History of Changes
Other Study ID Numbers:	NCI 04B3, NWU03-1-04, NCI 04B3
Study First Received:	February 9, 2006
Last Updated:	May 20, 2010
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Northwestern University:

breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Genistein
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Anticarcinogenic Agents
Protective Agents
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012