Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens

NCT04821141 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY00146320R01CA249437
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 6

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.

Conditions

Risk Reduction; Breast Cancer

Keywords

breast cancer, menopausal symptoms, hot flashes

Outcome Measures

Primary Outcomes (1)

• Change in FGV

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

  baseline to 6 months

Secondary Outcomes (1)

• Change in proliferation

  baseline to 6 months

Other Outcomes (2)

• Change in blood hormones

  baseline to 6 months

• change in gene expression

  baselne to 6 months

Study Arms (2)

Bazedoxifene plus conjugated estrogens immediately

EXPERIMENTAL

BZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing immediately.

Drug: Bazedoxifene and Conjugated Estrogens

Bazedoxifene plus conjugated estrogens wait list

OTHER

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.

Drug: Bazedoxifene and Conjugated Estrogens

Interventions

Bazedoxifene and Conjugated Estrogens DRUG

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

Also known as: BZA+CE

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

Eligibility Criteria

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

You may qualify if:

• Current vasomotor symptoms (hot-flashes, night sweats or both). These do not need to be frequent or severe but should occur at least once a week. Women who feel that they would likely need a supplement or be at high risk of withdrawal if they were randomized to waitlist because of vasomotor symptoms are not good candidates for this trial.
• Women must be in one of the four menopausal status categories, as defined below.
• Age 45-64 with an intact uterus and no periods in past 12 months. Amenorrhea is not thought to be due to endometrial ablation, Mirena IUD or other menses suppressing contraceptives. Category 1: Clinically Postmenopausal
• Age 45-64 with an intact uterus and no periods in past 2 months immediately preceding eligibility testing; but has not been amenorrheic for 12 months. Amenorrhea not thought to be due to endometrial ablation, Mirena IUD or other menses suppressing contraceptives. Category 2: Late menopause transition.
• Age 50-64 and prior hysterectomy, prior endometrial ablation with subsequent lack of periods, or menses suppression due to Mirena IUD or other types of contraceptives. Category 3: Menopause transition by symptoms; uterus not intact or menses suppression; age ≥50.
• Age 45-49 and prior hysterectomy, prior endometrial ablation with subsequent lack of periods, or menses suppression due to Mirena IUD or other types of contraceptives. Category 4: Menopause transition by symptoms uterus not intact or menses suppression; age 45-49.
• Must have at least one ovary.
• BMI: ≤ 38 kg/m2
• At least one breast without prior therapeutic radiation that can be assessed by Volpara® software.
• Chemistry profile showing reasonably normal renal and hepatic function: creatinine \<2.0 mg/dL, bilirubin \< 2.5 mg/dL, and albumin \> 3.4 g/dL within the past 12 months.
• Risk Factors/Level. Moderate risk of developing breast cancer based on having at least one of following:
• First or second degree relative with breast cancer age 60 or younger;
• A prior breast biopsy showing proliferative breast disease, including hyperplasia, atypical hyperplasia, or lobular carcinoma in situ
• or more prior biopsies regardless of benign histology
• Prior ER-PR- or low risk ER+ DCIS at minimum treated with surgical removal of lesion with or without radiation therapy.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Northwestern Medical Center

Chicago, Illinois, 60601, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• 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

• Carroll TJ, Abernethy PJ, Logan PA, Barber M, McEniery MT. Resistance training frequency: strength and myosin heavy chain responses to two and three bouts per week. Eur J Appl Physiol Occup Physiol. 1998 Aug;78(3):270-5. doi: 10.1007/s004210050419.

  PMID: 9721008 BACKGROUND

MeSH Terms

Conditions

Risk Reduction Behavior; Breast Neoplasms; Hot Flashes

Interventions

bazedoxifene; Estrogens, Conjugated (USP)

Condition Hierarchy (Ancestors)

Behavior; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Only designated biostatistician is aware of randomization assignment until after a subject is enrolled and assigned, Then assignment is unblinded and agents are open-label.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomization to immediate 6 months of BZA+CE versus wait list for 6 months followed by option to receive 6 months of BZA+CE.

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 29, 2021
• Study Start: December 14, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)