Pilot Study of the Effect of Duavee® on Benign Breast Tissue Proliferation

Study Overview
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Brief Summary
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The purpose of this study is to learn whether daily use of Duavee® is accepted and tolerated by peri- and post-menopausal women at moderate risk for development of breast cancer.

Detailed Description
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Duavee® is tissue specific estrogen complex of bazedoxifene plus conjugated estrogen which is FDA approved for relief of menopausal symptoms and prevention of osteoporosis in women with a uterus who have not been diagnosed with estrogen dependent neoplasia. The overall purpose of this research is to demonstrate in a preliminary fashion that despite reduction in menopausal symptoms, (Duavee®) does not increase and may decrease proliferation in benign breast tissue in a cohort of peri- or post-menopausal women at moderately increased risk for breast cancer. If this pilot shows rapid accrual, good retention, and lack of significant increase in the risk biomarker Ki-67 in benign breast tissue, a larger prevention trial is envisioned

Official Title
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Pilot Study of the Effect of Duavee® on Benign Breast Tissue Proliferation in Peri or Post-menopausal Women at Moderate Risk for Development of Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Duavee


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with vasomotor symptoms with a uterus who are postmenopausal or in late menopause transition Body Mass Index (BMI) <36 kg/m2 Class I-III mammogram within 6 months of Random Periareolar Fine Needle Aspiration (RPFNA); If Class 0 or 4, must be resolved with additional procedures If previously on oral contraceptives or hormone replacement, off for 8 weeks or more prior to baseline RPFNA; the exception is low dose vaginal hormones Confirmed moderate risk of developing breast cancer RPFNA results within study defined range Kidney and liver function within study defined range Willing and able to comply with study related procedures Exclusion Criteria: Previous biopsy showing evidence of breast cancer Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke History of renal or liver disease Prior ovarian or endometrial cancer Stopped or started hormone replacement within 8 weeks Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA Currently taking or have taken specific medications in the past 6 months Participation on any chemoprevention trial within 6 months Current illness which would make potential participant unsuitable for enrollment

Ages Eligible for Study
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Maximum Age: 61 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Duavee<br>Participants will be asked to take Duavee for 6 months while on the study. | Drug: Duavee<br>* Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))<br>* Other names: conjugated estrogens/bazedoxifene;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility for a Larger Trial | Outcome will be based on three separate factors used collectively to determine feasibility of the study and consideration of a subsequent larger trial. These are accrual rate (ability to accrue target number of subjects in a timely manner), dropout rate (frequency of subjects who are compliant and complete the intervention) and change in Ki-67 (increase vs decrease in percent of cells stained positive in the majority of subjects). Should accrual be inadequate or too slow; or if retention is too low; then a decision would be made not to proceed to a larger trial. Also, if there is evidence of an increase in proliferation (Ki-67) then no further studies would be planned. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ki-67 | Assessment by immunocytochemistry of the percent of breast epithelial cells staining positive. Per protocol, restricted to those subjects with baseline Ki-67 positivity >1.0% but < 4% | Change from Baseline to Month 6 | 
| Change in Fibroglandular Volume (FGV) | Assessment of mammograms for percent of breast defined as FGV by Volpara automated assessment. | Change from Baseline to Month 6 | 
| Change in Body Composition (Total Mass) | Assessment by Dual Energy X-ray Absorptivity (DEXA) | Change from Baseline to Month 6 | 
| Levels of Bazedoxifene in the Blood | Assessment of concentration of bazedoxifene in plasma by High-performance liquid chromatography (HPLC) | Month 6 |