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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Duavee

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Westwood, Kansas, United States, 66208
      • University of Kansas Medical Center Breast Cancer Prevention Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 61 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: Pfizer
• Investigators: Principal Investigator: Carol Fabian, MD, University of Kansas Medical Center

Publications and helpful links

General Publications

• Fabian CJ, Nye L, Powers KR, Nydegger JL, Kreutzjans AL, Phillips TA, Metheny T, Winblad O, Zalles CM, Hagan CR, Goodman ML, Gajewski BJ, Koestler DC, Chalise P, Kimler BF. Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study. Cancer Prev Res (Phila). 2019 Oct;12(10):711-720. doi: 10.1158/1940-6207.CAPR-19-0315. Epub 2019 Aug 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 31, 2016
• First Posted (Estimate): April 6, 2016

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: STUDY00002440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Results will be published in aggregate; no individual participant data will be made available.
• IPD Sharing Time Frame: 2021-2022
• IPD Sharing Access Criteria: upon request.
• IPD Sharing Supporting Information Type: Study Protocol