Genistein in Preventing Breast or Endometrial Cancer in Healthy Postmenopausal Women

Phase I Multiple Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of genistein may be effective in preventing breast or endometrial cancer.

PURPOSE: This randomized phase I trial is studying the effectiveness of genistein in preventing breast or endometrial cancer in healthy postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Endometrial Cancer
• Intervention / Treatment: Dietary supplement: Genistein; Dietary supplement: Placebo

Detailed Description

OBJECTIVES:

• Compare the effects of genistein vs placebo on DNA damage and apoptosis by conducting COMET, TUNEL, Caspase-3, and AP site assays in healthy postmenopausal women.
• Compare the effects of these drugs on gene expression in an estrogen-sensitive tissue by oligoarray profiling in these participants.
• Determine the effect of genistein on estrogenic effects by self-reported side effects, measurement of sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone, and estrogen levels, and expression of known estrogen-sensitive genes in these participants.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Participants are stratified according to their study ID numbers. Participants are randomized to 1 of 2 treatment arms.

• Arm I: Participants receive oral genistein twice daily on days 1-84.
• Arm II: Participants receive oral placebo twice daily on days 1-84. In both arms, treatment continues in the absence of dysplasia, malignancy, unacceptable toxicity, or gross noncompliance.

Participants are followed at days 7, 14, 28, 56, and 84 during study treatment and at day 28 after completion of study treatment.

PROJECTED ACCRUAL: A total of 30 participants (20 for arm I and 10 for arm II) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Healthy participants

  • Papanicolaou test (pap smear) normal within the past 13 months
  • Mammogram normal within the past 13 months
• No history of breast cancer
• Not at high-risk (5-year risk < 1.9%) for breast cancer according to NCI's Breast Cancer Risk Assessment Tool

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 45 to 70

Sex

• Female

Menopausal status

• Postmenopausal

  • Last spontaneous menstrual bleeding > 12 months ago

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• ALT and AST < 2 times normal
• No significant abnormality of the liver by physical exam

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• No significant cardiac disease
• No New York Heart Association class III or IV heart disease
• No significant abnormality of the heart by physical exam

Pulmonary

• No significant abnormality of the lung by physical exam

Other

• Body mass index < 35
• Follicle-stimulating hormone > 27 mIU/mL
• Thyroid or endocrine function test normal
• Alcohol intake ≤ 2 drinks/day or ≤14 drinks/week
• Not pregnant
• No intermediate equol values (≥10 ug/L to ≤ 20 ug/L) on soy challenge
• No history of seizures
• No significant abnormality of the spleen or other abdominal organs by physical exam
• No neurologic abnormality by physical exam
• No significant metabolic abnormality on the biochemical screen
• No history of substance abuse or addiction
• No tobacco use
• No diets containing > 20 mg of genistein/day or > 40 mg isoflavone/day
• No known intolerance to soy
• No other serious medical illness
• No active malignancy or malignancy initially diagnosed within the past 2 years except curatively treated nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 2 years since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• More than 3 months since prior hormonal or estrogen therapy
• More than 3 months since prior tamoxifen or other selective estrogen-receptor modulators
• More than 1 month since prior supplements containing phytoestrogens or that have estrogenic side effects (soy isoflavones or PC-SPECS)

• No concurrent thyroid medication

  • Other concurrent endocrine medication allowed provided medication was initiated ≥ 3 months before study entry AND participant has been on a stable regimen for the past 3 months

Radiotherapy

• Not specified

Surgery

• No prior hysterectomy or oophorectomy

Other

• More than 3 months since prior antibiotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Genistein	Dietary supplement: Genistein; oral Genistein twice daily on days 1-84; Other Names: PTI G-2535
Placebo Comparator: Arm II; Placebo	Dietary supplement: Placebo; oral Placebo twice daily on days 1-84

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of genistein on DNA and apoptosis	Compare the effects of genistein vs placebo on DNA damage and apoptosis by conducting COMET, TUNEL, Caspase-3, and AP site assays in healthy postmenopausal women.	112 days

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven H. Zeisel, MD, PhD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

General Publications

• Pop EA, Fischer LM, Coan AD, Gitzinger M, Nakamura J, Zeisel SH. Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: a phase I clinical trial. Menopause. 2008 Jul-Aug;15(4 Pt 1):684-92. doi: 10.1097/gme.0b013e318167b8f2.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): July 1, 2005
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: December 8, 2004
• First Submitted That Met QC Criteria: December 8, 2004
• First Posted (Estimate): December 9, 2004

Study Record Updates

• Last Update Posted (Estimate): May 21, 2013
• Last Update Submitted That Met QC Criteria: May 17, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: breast cancer; endometrial cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Anticarcinogenic Agents; Phytoestrogens; Genistein
• Other Study ID Numbers: UNC-GCRC-2107; CDR0000393450 (Other Identifier: PDQ number)