Bazedoxifene + Conjugated Estrogens for Breast Cancer Risk Reduction
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18 - 65
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Kansas Medical Center
Must not be taking: Anticoagulants, Systemic hormones, Tamoxifen
Disqualifiers: Thromboembolism, BRCA1/2 mutation, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial tests a combination of two medications, bazedoxifene and conjugated estrogens, in women at risk for breast cancer who also have menopausal hot flashes. The treatment aims to reduce these symptoms and possibly lower cancer risk. Researchers will compare changes in breast tissue and hormone levels over several months between those taking the medication and those who are not. Bazedoxifene paired with conjugated estrogens is the first combination approved by the FDA for treating menopausal symptoms.
Will I have to stop taking my current medications?
If you are currently taking oral contraceptives or systemic hormone replacement therapies, you must stop them at least 8 weeks before starting the trial. However, you can continue using low-dose vaginal hormones for vaginal dryness if you've been on them for at least 2 weeks before the trial.
Is Bazedoxifene + Conjugated Estrogens safe for humans?
Bazedoxifene combined with conjugated estrogens has been studied in several trials and is generally considered safe for treating menopausal symptoms and preserving bone health. It has been shown to have cardiovascular safety and does not increase the risk of uterine bleeding or breast pain, which are common with other hormone therapies.12345
How is the drug Bazedoxifene + Conjugated Estrogens unique for breast cancer risk reduction?
Bazedoxifene + Conjugated Estrogens is unique because it combines a selective estrogen receptor modulator (Bazedoxifene) with estrogens to reduce breast cancer risk by minimizing estrogen's stimulatory effects on breast tissue, unlike traditional hormone therapies that often include progestins.34678
Eligibility Criteria
Women aged 45-64 with moderate risk of breast cancer, experiencing menopausal hot flashes at least weekly, and not currently on certain hormone treatments or having specific health conditions. Participants must have a BMI ≤ 38 kg/m2 and at least one breast assessable by Volpara software without prior radiation.Inclusion Criteria
My kidney and liver tests are within normal ranges.
Must be in one of the four menopausal status categories
I am a woman aged 45-60, or 61-64 with a recent mammogram showing dense breast tissue.
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Exclusion Criteria
Sufficiently distressed by vasomotor symptoms that they do not believe they would be able to remain on study for 6 months without additional medications
My breast condition is identified as pleomorphic LCIS.
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
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive BZA (20 mg) plus CE (0.45 mg) daily for 6 months
6 months
Baseline and 6-month visits for imaging and biomarker assessments
Waitlist Control
Participants are on a waitlist for 6 months before starting treatment
6 months
Follow-up
Participants are monitored for changes in biomarkers and safety after treatment
4 weeks
Treatment Details
Interventions
- Bazedoxifene (Selective Estrogen Receptor Modulator (SERM))
- Conjugated Estrogens (Estrogen)
Trial OverviewThe trial is testing if Bazedoxifene plus Conjugated Estrogens can reduce the risk of developing breast cancer in women with vasomotor symptoms. It measures changes in fibroglandular volume and cell proliferation over six months against a control group.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Bazedoxifene plus conjugated estrogens wait listExperimental Treatment1 Intervention
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.
Group II: Bazedoxifene plus conjugated estrogens immediatelyExperimental Treatment1 Intervention
BZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing immediately.
Bazedoxifene is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Duavee for:
- Moderate to severe vasomotor symptoms associated with menopause
- Prevention of postmenopausal osteoporosis
🇪🇺 Approved in European Union as Duavive for:
- Treatment of estrogen deficiency symptoms in postmenopausal women with an intact uterus
- Prevention of osteoporosis in postmenopausal women at high risk of future fractures
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
Dana Farber Cancer InstituteBoston, MA
University of Kansas Medical CenterKansas City, KS
Northwestern Medical CenterChicago, IL
More Trial Locations
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Who Is Running the Clinical Trial?
University of Kansas Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. [2015]Five randomized, phase-3 trials demonstrated the efficacy and safety of conjugated estrogens/bazedoxifene (CE/BZA) in treating menopausal symptoms and preserving bone. This pooled analysis of these studies describes the cardiovascular safety of CE/BZA.
Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women. [2013]Bazedoxifene/conjugated estrogens (BZA/CE) has demonstrated efficacy in improving vasomotor and vulvar/vaginal atrophy symptoms in postmenopausal women. This study evaluated the endometrial safety of BZA/CE and effects on bone mineral density (BMD) compared with CE/medroxyprogesterone acetate (MPA) and placebo.
Conjugated estrogen/bazedoxifene tablets for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. [2016]Conjugated estrogen/bazedoxifene (CE/BZA) therapy represents a new, progestin-free treatment in the management of postmenopausal health. CE/BZA pairs CE with the selective estrogen receptor modulator, BZA. The rationale for the development of CE/BZA was that BZA, acting primarily as a selective estrogen receptor degrader in uterine and breast tissue, would sufficiently inhibit the proliferative effects of CE on the endometrium. The absence of a progestin would reduce the incidence of uterine bleeding, breast pain and increased breast density associated with progestin-containing hormone therapy. CE/BZA has been evaluated in five multicenter, randomized, double-blind, placebo-controlled, and active-controlled Phase III trials known as the SMART trials. CE/BZA has been shown to maintain the established benefits of estrogen therapy for treatment of vasomotor symptoms and prevention of a loss in bone mineral density (bone mass), while minimizing certain estrogenic effects, particularly in the uterine endometrium and breast.
Bazedoxifene for HRT? [2017]Duavive (Pfizer) is a modified-release formulation of conjugated oestrogens plus bazedoxifene acetate (a selective oestrogen receptor modulator). It is licensed for treatment of oestrogen deficiency symptoms in postmenopausal women with a uterus for whom treatment with progestogen-containing therapy is not appropriate.1,2 It was licensed by the European Medicines Agency (EMA) in 2014 and launched in the UK in July 2016.1,3 Here, we review the evidence on efficacy and safety of conjugated oestrogens/bazedoxifene and consider its place in the management of symptoms associated with the menopause.
Most bothersome symptom in women with genitourinary syndrome of menopause as a moderator of treatment effects. [2018]Conjugated estrogens/bazedoxifene (CE/BZA) is indicated to treat moderate/severe menopausal vasomotor symptoms and prevent postmenopausal osteoporosis. This analysis examines the impact of the most bothersome vaginal symptom at baseline on effects of CE/BZA.
Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. [2012]Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen receptor modulator (SERM) being developed for the prevention and treatment of osteoporosis. Preclinical studies on bazedoxifene have demonstrated estrogen agonist effects on the skeleton and lipid metabolism but not on breast and uterine endometrium. In combination with estrogen, bazedoxifene antagonizes the stimulatory action of estrogens on proliferation of breast cancer cells and endometrium. Phase III clinical studies have shown favorable effects on the skeleton without stimulation of endometrium and breast. Bazedoxifene prevents bone loss in postmenopausal women without osteoporosis and reduces vertebral fractures in women with postmenopausal osteoporosis. In women at high risk of fracture with multiple risk factors, bazedoxifene reduces nonvertebral fracture risk in post-hoc analysis. Bazedoxifene in combination with conjugated estrogens represents a new form of therapeutic agents for the treatment of postmenopausal symptoms and prevention of postmenopausal osteoporosis. Clinical trials with bazedoxifene/conjugated estrogens have shown beneficial effects on bone mineral density and bone turnover markers with improvement in vasomotor symptoms and little or no stimulation of breast and endometrium.
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. [2019]Bazedoxifene acetate (WAY-140424; TSE-424) is an investigational non-steroidal indole-based selective estrogen receptor modulator (SERM) - also classified as an estrogen agonist/antagonist - that is being developed as a daily oral drug for the prevention and treatment of postmenopausal osteoporosis (PMO). Clinical studies have shown favorable effects on the skeleton, with prevention of bone loss in postmenopausal women without osteoporosis and reduction in vertebral fracture risk in women with PMO, without stimulation of endometrium or breast. Bazedoxifene combined with conjugated estrogens is an investigational tissue-selective estrogen complex, the first in a new class of therapeutic agents that pairs a selective estrogen receptor modulator with estrogens. Clinical trials with bazedoxifene/conjugated estrogens in postmenopausal women have shown skeletal benefit with improvement in menopausal vasomotor symptoms and little or no stimulation of endometrial or breast tissue. Bazedoxifene/conjugated estrogens is a potential agent for the prevention of PMO and control of menopausal symptoms.
Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. [2021]Concerns about increased breast cancer risk with estrogen and progestin therapy have led to an increased interest in progestin alternatives. The main objective of this study was to determine if bazedoxifene acetate (BZA), a new selective estrogen receptor modulator, will antagonize the proliferative and transcriptional effects of conjugated equine estrogens (CEE) in the breast.