Genistein in Preventing Breast or Endometrial Cancer in Healthy Postmenopausal Women

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Endometrial Cancer

Intervention / Treatment
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* Dietary Supplement: Genistein
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Genistein | Dietary Supplement: Genistein<br>* oral Genistein twice daily on days 1-84<br>* Other names: PTI G-2535;|
| Placebo Comparator: Arm II<br>Placebo | Dietary Supplement: Placebo<br>* oral Placebo twice daily on days 1-84<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, endometrial cancer