Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens

Phase 2

Recruiting

• Conditions: Risk Reduction; Breast Cancer
• Interventions: Drug: Bazedoxifene and Conjugated Estrogens

• Registration Number: NCT04821141
• Lead Sponsor: University of Kansas Medical Center

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-03-18
• Study First Submitted QC: 2021-03-25
• Study First Posted: 2021-03-29
• Study Start: 2021-12-14
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-18
• Primary Completion: 2026-07-31
• Study Completion: 2027-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bazedoxifene plus conjugated estrogens immediately	Bazedoxifene and Conjugated Estrogens	BZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing immediately.
Bazedoxifene plus conjugated estrogens wait list	Bazedoxifene and Conjugated Estrogens	No intervention for initial 6 months (wait list), then BZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing 6 months after enrollment. Optional on the part of subject.

Primary Outcome Measures

Name	Time	Method
Change in FGV	baseline to 6 months	Change in fibroglandular volume assessed on 3-D digital mammogram by Volpara software.

Secondary Outcome Measures

Name	Time	Method
Change in proliferation	baseline to 6 months	change in percent of breast epithelial cells staining positive for Ki-67 by immunocytochemistry

Trial Locations

Locations (5)

Northwestern Medical Center; 🇺🇸 Chicago, Illinois, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States