Pilot Study of Bazedoxifene Plus Conjugated Estrogen on Imaging and Blood Biomarkers

NCT04821375 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: Study00146761
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Pilot study to test feasibility of 6 months of bazedoxifene (BZA) plus conjugated estrogens (CE) to modulate breast MRI parameters.

Conditions

Increased Risk for Development of Breast Cancer

Keywords

breast cancer

Outcome Measures

Primary Outcomes (1)

• Number of potential participants who consent to enrollment

  Trial design is acceptable to potential subjects, as evidenced by participation

  Enrollment

Secondary Outcomes (2)

• Change in breast background parenchymal enhancement (BPE)

  6 months

• Change in fibroglandular volume (FGV)

  6 months

Study Arms (2)

Bazedoxifene plus conjugated estrogens immediately

EXPERIMENTAL

Immediate receipt of 6 months of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg) taken together daily.

Drug: bazedoxifene plus conjugated estrogens

Bazedoxifene plus conjugated estrogens wait list

OTHER

After a 6-month waiting period, receipt of 6 months of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg) taken together daily.

Drug: bazedoxifene plus conjugated estrogens

Interventions

bazedoxifene plus conjugated estrogens DRUG

6 months of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg) taken together daily.

Also known as: BZA+CE

Bazedoxifene plus conjugated estrogens immediately; Bazedoxifene plus conjugated estrogens wait list

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women who report vasomotor symptoms (hot flashes or night sweats or both).
• No menstrual periods for at least 60 days.
• Age 45-65. Women age 45-49 with prior hysterectomy or endometrial ablation with rare or no periods due to ablation must have a Follicle Stimulating Hormone (FSH) of 25 mIU/ml or higher to be eligible.
• BMI \<36 kg/m2
• Risk Factors/Level. Moderate risk of developing breast cancer based on either by having any one or more of the following:
• First or 2nd degree relative with breast cancer
• Known carrier of moderate to high penetrance germline mutation
• Prior breast biopsy showing proliferative breast disease or multiple prior biopsies
• High mammographic density (Volpara® categories c or d or BIRADS density assessment as heterogeneously or extremely dense (c or d).
• IBIS Breast Cancer Risk Evaluation Version 8 (http://www.emstrials.org/riskevaluator/). 10-year relative risk of \>2X that for the population for age group.
• Prior mammogram must have at least a Volpara® fibroglandular volume of 80 cm3 or BIRADs b, c, or d category density and/or investigator estimated visual dense area of at least 25%. The entire breast must be incorporated in a single view for both the right and left breast. (i.e., women whose breasts are so large that the images must be captured as a mosaic are not eligible). If no prior mammogram, but breast density is readily appreciated and documented on physical exam, a study-provided 3D mammogram with Volpara® software must be performed to document above eligibility criterion. It will then constitute the baseline mammogram.
• Willing to comply with study procedures:
• Have blood drawn for screening tests - comprehensive metabolic panel (plus FSH if age 45-49 and no uterus or endometrial ablation)
• Have blood drawn to archive serum for assay of estradiol, testosterone, progesterone, sex hormone binding globulin (SHBG), FSH at baseline and 6-month visits (and 12 months for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months).
• Undergo a history, physical, and breast exam at baseline and 6-month visits (and 12 months for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months). History, physical exam and breast exam performed by a study-associated clinician within 3 months prior to enrollment may be substituted for baseline evaluations.

You may not qualify if:

• Risk: A prior biopsy showing pleomorphic lobular or ductal carcinoma in situ or invasive breast cancer.
• Medical Conditions:
• Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke
• History of renal or liver disease
• Prior invasive ovarian or endometrial cancer
• Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for BZA+CE.
• Medications
• Taking systemic hormones within two months (eight weeks) prior to baseline MRI and mammogram.
• Taking systemic hormones within two months (eight weeks) prior to baseline MRI and mammogram.
• Taking tamoxifen, raloxifene, Duavee®, or any selective estrogen receptor modulator, or an aromatase inhibitor within 12 months prior to baseline MRI and mammogram.
• Mammogram with Volpara® software and/or abbreviated MRI interpreted as concerning for cancer - unless recommended breast biopsy has been performed and confirmed as benign.
• Dispensing of BZA+CE for those randomized to receive it immediately does not occur within 3 months of baseline MRI.
• Unwilling to comply with future study procedures.
• Started hormone replacement, selective estrogen receptor modulator, or aromatase inhibitor after baseline studies performed but prior to randomization.

Sponsors & Collaborators

• Carol Fabian, MD: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Related Publications (1)

• 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.

  PMID: 31420361 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

bazedoxifene; Estrogens, Conjugated (USP)

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Carol J Fabian, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Only a designated biostatistician and investigational pharmacy personnel will be aware randomization until after a subject is enrolled, and then all involved in the study will be aware of assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Randomized at enrollment to either immediate study agent or study agent after a 6-months wait.

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 29, 2021
• Study Start: December 2, 2021
• Primary Completion: May 20, 2024
• Study Completion: December 31, 2024
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)