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About
Women at risk for development of breast cancer and experiencing vasomotor menopausal symptoms (hot flashes) will be randomized to bazedoxifene (BZA) plus conjugated estrogens (CE) for 6 months versus a wait list control. Two risk factors for development of breast cancer will be studied pre-study and after 6 months: fibroglandular volume (FGV) on mammogram as assessed by Volpara software and proliferation by Ki-67 immunocytochemistry in benign breast tissue acquired by random periareolar fine needle aspiration (RPFNA). Change in biomarkers will be compared between groups.
Full description
Phase IIB trial of 6 months of BZA 20 mg +CE 0.45 mg (subsequently designated as BZA+CE) vs a waitlist control. Trial is informed by prior results of a single arm trial that used Duavee® (combination of BZA+CE that is FDA-approved for relief of hot flashes). Since Duavee® is currently not available commercially, the two separate components are used instead. Breast imaging, benign breast tissue by RPFNA, and blood for biomarkers will be obtained at baseline and at 6 months using similar assessment techniques. The primary endpoint is the difference between the BZA+CE and control groups for absolute change from baseline to 6 months in the risk biomarker fibroglandular volume (FGV). Volpara® fully automated assessments overcome the interpretive variance inherent in subjective assessments. Additional endpoints include changes in benign breast epithelial immunolabeling for Ki-67, estrogen receptor alpha (ERα), progesterone receptor (PR), and anterior gradient-2 protein (AGR2); and systemic levels of bioavailable hormones, IGF-1, IGFBP3, and measures of insulin sensitivity. The modifying effects of baseline BMI, visceral adipose, and plasma BZA concentrations on markers will be studied.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria for Baseline Mammogram and RPFNA Women ages 45 - 60 or ages 61-64 if their last mammogram was described as heterogeneously or extremely dense.
Current vasomotor symptoms (hot-flashes, night sweats or both). These do not need to be frequent or severe but should occur at least once a week. Women who feel that they would likely need a supplement or be at high risk of withdrawal if they were randomized to waitlist because of vasomotor symptoms are not good candidates for this trial.
Women must be in one of the four menopausal status categories, as defined below.
Must have at least one ovary.
BMI: ≤ 38 kg/m2
At least one breast without prior therapeutic radiation that can be assessed by Volpara® software.
Chemistry profile showing reasonably normal renal and hepatic function: creatinine <2.0 mg/dL, bilirubin < 2.5 mg/dL, and albumin > 3.4 g/dL within the past 12 months.
Risk Factors/Level. Moderate risk of developing breast cancer based on having at least one of following:
Vaginal Hormones: Low dose vaginal hormones, such as Estring(®, Vagifem®, Imvexy®, or 0.5 gram or less of conjugated estrogen vaginal cream twice weekly or less often, for vaginal dryness and dyspareunia may be continued at the same dose.
Systemic Hormones: If previously on oral contraceptives or systemic hormone replacement such as pills, transdermal patches, oral troches, or injections, must be off for 8 weeks or more prior to baseline mammogram and RPFNA.
Exclusion Criteria for Screening
Conditions:
Medications
Inclusion Criteria for Randomization Study mammograms
RPFNA must be performed and specimen received at KUMC in good condition. RPFNA specimen must have ductal/lobular epithelial cells on Thinprep® slides; but there is no requirement for a specific cell number, value for Ki-67, or cytomorphology.
Blood must be drawn prior to randomization and sent to KUMC.
Complete Menopause specific quality of life questionnaire, information for hot flash score.
Willing to comply with study procedures.
Participants at KUMC: Dual energy x-ray absorptiometry (iDXA)
Pregnancy test for women <age 55 with intact uterus
Exclusion Criteria for Randomization Intercurrent illness which makes potential participant unsuitable for study; Starting hormone replacement therapy (prescription pills, injections, patches) between mammogram/RPFNA and enrollment on study.
Primary purpose
Allocation
Interventional model
Masking
120 participants in 2 patient groups
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Central trial contact
Carol J Fabian, MD; Bruce Kimler, PhD
Data sourced from clinicaltrials.gov
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