Phase I Multiple Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women
45 Years
70 Years
Female
Breast Cancer, Endometrial Cancer
Trial Information
Phase I Multiple Dose Clinical Study of Soy Isoflavones in Healthy, Post-Menopausal Women
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Prevention
Outcome Measure:
Efficacy of genistein on DNA and apoptosis
Outcome Description:
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.
Outcome Time Frame:
112 days
Safety Issue:
No
Principal Investigator
Steven H. Zeisel, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UNC Lineberger Comprehensive Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
UNC-GCRC-2107
NCT ID:
NCT00099008
Start Date:
March 2004
Completion Date:
July 2006
Related Keywords:
- Breast Cancer
- Endometrial Cancer
- breast cancer
- endometrial cancer
- Breast Neoplasms
- Endometrial Neoplasms
- Sarcoma, Endometrial Stromal
- Adenoma
Name | Location |
|---|---|
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
