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Risk ReductionPhase 2NCT04821141

Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens

A Phase 2 study testing Bazedoxifene and Conjugated Estrogens in people with Risk Reduction and Breast Cancer, run by University of Kansas Medical Center at 6 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 45 to 64 years, women onlyHealthy volunteers can take part
Conditions the study is for
Risk Reduction, Breast Cancer
What is being tested?
Bazedoxifene and Conjugated Estrogens
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
6 sitesUnited States
Study dates
14 Dec 2021to 31 Jul 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 64 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 3D mammograms must be performed within 3 months of RPFNA. Women whose breast size require mosaic views will not be eligible.
  • Clinical mammogram Interpretation: Mammograms read out as Class 0 or IV must be resolved with additional procedures prior to randomization or entry on intervention phase. Women having a recent benign biopsy subsequent to a BIRADS IV mammogram with continuing BIRADs IV on baseline mammogram for Volpara assessment may be entered if other clinical assessments (i.e., MRI) is judged as not worrisome for cancer and/or re-biopsy or re-excision is not being considered by the patient's clinical team.
  • Raw data DICOM files must be available for generation of Volpara Score Card. Study consent must be signed prior to sending the DICOM files to the researcher server as these files will contain patient identifiers.
  • A Volpara score card must be generated for at least 1 breast and the FGV must meet minimal requirements for BMI.
  • If BMI < 25 kg/m2, then FGV must average at least 20 cm3 per breast (i.e., ≥20 cm3 if only one breast evaluable and ≥40 cm3 total if both breasts evaluable).
  • If BMI is 25-38 kg/m2 then FGV must be at least 30 cm3 per breast (i.e., ≥30 cm3 if only one breast evaluable and ≥60 cm3 total if both breasts evaluable).
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  • The Volpara® "Score Card" must be sent to KUMC prior to randomization.
  • 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.

Who cannot join

  • Conditions:
  • Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, stroke, or myocardial infarction. Note that individuals with a prior septic embolus only with no evidence of a clotting disorder are not excluded if cleared by their cardiologist or internist.
  • Prior bilateral oophorectomy
  • BRCA1/2 deleterious mutation
  • LCIS specifically designated as pleomorphic in the pathology report
  • Prior high-risk ER+ and/or PR+ DCIS, defined as high grade, > 2 cm in diameter or diagnosed at age < 50.
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  • Prior DCIS with cancer cells at inked margin where there was not an additional resection.
  • Prior invasive breast cancer
  • Prior invasive uterine or ovarian cancer
  • Current renal or liver disease or clinically significant abnormalities of liver and renal function tests.
  • Known hypoparathyroidism or recent history of triglycerides > 300 mg/dl.
  • Women are sufficiently distressed by their vasomotor symptoms, such that they do not believe they would be able to remain on study for 6 months without additional medications if their hot flashes were not relieved.
  • Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA or treatment with BZA+CE.
  • Medications
  • Current anticoagulant use (must have discontinued for 3 weeks prior to FNA)
  • Taking oral or transdermal systemic hormones within two months (eight weeks) prior to baseline blood, imaging studies or RPFNA. (Note that continued use of vaginal low dose hormonal preparations for dyspareunia is allowed if the woman had been on for at least 2 weeks prior to baseline testing)
  • Taken tamoxifen, raloxifene, or an aromatase inhibitor within 6 months of baseline blood imaging or RPFNA

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern Medical Center

    Chicago, Illinois, 60601

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • City of Hope Medical Center

    Duarte, California, 91010

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of California San Francisco

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: Randomized IIB Study of the Effect of Bazedoxifene Plus Conjugated Estrogens on Breast Imaging and Tissue Biomarkers in Peri or Post-Menopausal Women at Increased Risk for Development of Breast Cancer

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.

Read the 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.

Being tested
Bazedoxifene and Conjugated Estrogens
Keywords
breast cancer, menopausal symptoms, hot flashes
Medical subject headings
Risk Reduction Behavior, Breast Neoplasms, Hot Flashes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bazedoxifene and Conjugated EstrogensDrug

    Also called BZA+CE

    BZA (20 mg) plus CE (0.45 mg) taken together once daily

Study groups in NCT04821141
Study groupRoleWhat they receive
Bazedoxifene plus conjugated estrogens immediatelyExperimentalBZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing immediately.
Receives: Drug: Bazedoxifene and Conjugated Estrogens
Bazedoxifene plus conjugated estrogens wait listOtherNo 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.
Receives: Drug: Bazedoxifene and Conjugated Estrogens

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in FGV

    Change in fibroglandular volume assessed on 3-D digital mammogram by Volpara software.

    Measured: baseline to 6 months

Secondary outcomes (1)
  1. Change in proliferation

    change in percent of breast epithelial cells staining positive for Ki-67 by immunocytochemistry

    Measured: baseline to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2021
  2. Study start14 Dec 2021
  3. Primary completionOct 2026 (estimated)
  4. Study completion31 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomization to immediate 6 months of BZA+CE versus wait list for 6 months followed by option to receive 6 months of BZA+CE.
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04821141
Sponsor's protocol ID
STUDY00146320
Other IDs
R01CA249437
Status last verified
Sep 2026
First submitted
18 Mar 2021
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 31420361
  • Gajewski BJ, Kimler BF, Koestler DC, Mudaranthakam DP, Young K, Fabian CJ. A novel Bayesian adaptive design incorporating both primary and secondary endpoints for randomized IIB chemoprevention study of women at increased risk for breast cancer. Trials. 2022 Dec 5;23(1):981. doi: 10.1186/s13063-022-06930-5.

    PubMed 36471449
  • Fabian CJ, Mudaranthakam DP, Gajewski B, Young K, Winblad O, Khan SA, Garber JE, Esserman LJ, Yee LD, Nye L, Powers KR, Ranallo L, Kreutzjans AL, Pittman K, Altman C, Metheny T, Zelenchuk A, Komm BS, Kimler BF. Overcoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control. Contemp Clin Trials. 2024 Nov;146:107697. doi: 10.1016/j.cct.2024.107697. Epub 2024 Sep 17.

    PubMed 39293780

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bazedoxifene and Conjugated Estrogens in people with Risk Reduction and Breast Cancer, run by University of Kansas Medical Center at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in FGV (time frame: baseline to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04821141, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

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