Duavee for Breast Cancer

No longer recruiting at 10 trial locations

Overseen By Melissa Lazar, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: HRT, SERM, Aromatase inhibitors

Disqualifiers: Active malignancy, Thrombosis, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the medication Duavee® (Conjugated Estrogens/Bazedoxifene) can safely reduce the risk of developing breast cancer in women with ductal carcinoma in situ (DCIS), a non-invasive form of breast cancer. Participants will receive either the medication or a placebo to assess Duavee®'s effect on breast tissue markers linked to cancer risk. Postmenopausal women diagnosed with ER(+) DCIS may be suitable for this trial. The goal is to determine the medication's safety and potential benefits in this context. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are on hormone replacement therapy, selective estrogen receptor modulators, or aromatase inhibitors, you must stop them 30 days before a diagnostic core needle biopsy. Additionally, if you are taking medications that strongly affect certain liver enzymes, you need a washout period of at least 7 days or 5 half-lives of the drug, whichever is shorter.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the medication Duavee, a combination of conjugated estrogens and bazedoxifene, is generally well-tolerated by patients. Studies conducted over two years found that this treatment reduced hot flashes and other menopause symptoms without raising the risk of certain health issues. Specifically, there was no increase in breast cancer cases among users. However, there might be a slight increase in the risk of cancer or thickening of the uterine lining. The FDA has approved this treatment for managing menopause symptoms in healthy postmenopausal women, indicating it is considered safe for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard breast cancer treatments that typically involve chemotherapy or hormone therapy, the investigational treatment using conjugated estrogens/bazedoxifene offers a novel approach by combining two types of active ingredients. This combination aims to potentially reduce cancer cell growth while also minimizing estrogen receptor activation, which can be a concern in hormone-sensitive cancers. Researchers are excited because this treatment could provide a dual benefit: addressing the cancer more directly while possibly offering a better side effect profile compared to traditional hormone therapies. By leveraging both conjugated estrogens and bazedoxifene, the treatment might offer a new mechanism that enhances effectiveness and tolerability.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

In this trial, participants will receive either Duavee® (a combination of conjugated estrogens and bazedoxifene) or a placebo. Research has shown that Duavee® may help lower the risk of breast cancer. One study found that women taking Duavee® experienced positive changes in several breast cancer risk indicators over six months. Another study associated the estrogens in Duavee® with a 22% lower risk of breast cancer compared to a placebo. While primarily used for menopausal symptoms, Duavee® also shows promise in improving metabolic health and reducing breast cancer risk, particularly in women with obesity. Overall, these findings suggest that Duavee® could be effective in lowering breast cancer risk. ^{2 3 5 6 7}

Who Is on the Research Team?

Swati Kulkarni, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

Postmenopausal women aged 18-79 with newly diagnosed ER (+) DCIS of the breast, scheduled for surgery. Participants must be able to swallow pills, sign consent forms, and have normal organ/marrow function. Excluded are those on certain drugs, with invasive breast cancer or other serious conditions like blood clots or active second cancers.

Inclusion Criteria

I am a woman with a new ER+ DCIS diagnosis planning for surgery.

The size of the DCIS on the imaging meets the standards set by the hospital.

My cancer's growth markers are similar to those in a specific breast condition.

Exclusion Criteria

You have had allergic reactions to similar medicines as CE/BZA.

I have another active cancer besides non-melanoma skin cancer.

You cannot take any other experimental medications. If you were taking one before, you need to stop for at least 4 weeks before you can join the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive conjugated estrogens/bazedoxifene or placebo orally once daily for 28 +/- 7 days

4-5 weeks

Daily oral administration

Surgery

Participants undergo surgery following the treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Conjugated Estrogens/Bazedoxifene
• Placebo

Trial Overview The PROMISE Study tests if Duavee (conjugated estrogens/bazedoxifene), approved for menopause symptoms but not for DCIS in postmenopausal women, affects breast tissue markers and is safe. It includes a placebo group and examines quality-of-life impacts through questionnaires.

How Is the Trial Designed?

Group I: Arm I (conjugated estrogens/bazedoxifene) Experimental Treatment 5 Interventions

Patients receive conjugated estrogens/bazedoxifene orally (PO) once daily (QD) for 28 +/- 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

Group II: Arm II (placebo) Placebo Group 5 Interventions

Patients receive placebo PO QD for 28 +/- 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

University of Chicago - Department for Cancer Research

Collaborator

Trials

1

Recruited

140+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a 20-month study involving 95 ovariectomized cynomolgus macaques, the combination of bazedoxifene acetate (BZA) and conjugated equine estrogens (CEE) significantly reduced breast tissue proliferation and density compared to CEE alone, suggesting a potential for lower breast cancer risk.

BZA acted as an estrogen antagonist in the breast, effectively blocking the effects of CEE on estrogen receptor activity and gene expression related to cell proliferation, indicating that BZA could be a safer alternative to traditional estrogen and progestin therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. Ethun, KF., Wood, CE., Register, TC., et al.[2021]

A pooled analysis of five phase-3 trials involving 4868 healthy, non-hysterectomized postmenopausal women showed that conjugated estrogens/bazedoxifene (CE/BZA) has an acceptable cardiovascular safety profile, with low rates of venous thromboembolic events (VTEs) and comparable rates of stroke and coronary heart disease (CHD) to placebo.

The incidence of VTEs was very low across different doses of CE/BZA, with rates of 0.3 to 0.7 per 1000 woman-years, indicating that CE/BZA is a safe option for managing menopausal symptoms without significantly increasing cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. Komm, BS., Thompson, JR., Mirkin, S.[2015]

Duavive, a combination of conjugated oestrogens and bazedoxifene acetate, is effective for treating estrogen deficiency symptoms in postmenopausal women who cannot use progestogen therapy, highlighting its targeted approach for this specific patient group.

Since its approval by the European Medicines Agency in 2014 and launch in the UK in 2016, Duavive has been reviewed for both efficacy and safety, establishing its role in managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene for HRT? [2017]

Bazedoxifene acetate is an investigational oral drug that effectively prevents bone loss and reduces vertebral fracture risk in postmenopausal women, without affecting the endometrium or breast tissue.

When combined with conjugated estrogens, bazedoxifene shows promise in improving menopausal symptoms while providing skeletal benefits, making it a potential treatment for postmenopausal osteoporosis and related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. Lewiecki, EM.[2019]

In a study of 459 nonhysterectomized postmenopausal women, treatment with bazedoxifene (BZA) and conjugated estrogens (CE) for one year significantly improved sleep quality and health-related quality of life (HRQoL) compared to placebo.

Both BZA/CE and CE/medroxyprogesterone acetate (MPA) showed notable improvements in sleep parameters and MENQOL scores at 12 months, indicating their effectiveness in managing symptoms related to menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep parameters and health-related quality of life with bazedoxifene/conjugated estrogens: a randomized trial. Pinkerton, JV., Pan, K., Abraham, L., et al.[2022]

Bazedoxifene acetate is an effective oral treatment for preventing and treating osteoporosis in postmenopausal women, showing positive effects on bone health without stimulating breast or uterine tissue.

In combination with conjugated estrogens, bazedoxifene improves bone mineral density and reduces fracture risk while also alleviating menopausal symptoms, making it a promising option for women at high risk of osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. Kung, AW., Chu, EY., Xu, L.[2012]

Endocrine therapy, particularly with tamoxifen, is a key treatment for women with steroid receptor-positive breast cancers, significantly lowering the risk of recurrence and death.

For premenopausal women, ovarian suppression is a crucial option, while postmenopausal women may benefit from aromatase inhibitors, highlighting the need for ongoing research into the best treatment sequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of breast cancer. Endocrine therapy]. Mouridsen, HT., Andersen, J.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6774863/

Effect of Bazedoxifene and Conjugated Estrogen (Duavee ... We demonstrated excellent retention and favorable change in multiple risk biomarkers for breast cancer with 6 months of Duavee® in peri and ...

2. insight.jci.org insight.jci.org/articles/view/182694

Metabolic and transcriptional effects of bazedoxifene ... These data support the use of BZA/CE to improve metabolic health and reduce breast cancer risk in individuals with obesity.

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04821141

Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens Women at risk for development of breast cancer and experiencing vasomotor menopausal symptoms (hot flashes) will be randomized to bazedoxifene ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37449720/

Comparative safety of conjugated estrogens/bazedoxifene ... CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1551714424002805

Bazedoxifene and conjugated estrogens vs waitlist control Indeed, in the Women's Health Initiative, conjugated estrogens alone, compared to placebo, was associated with a 22 % reduction in risk for breast cancer and 40 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10389232/

Comparative safety of conjugated estrogens/bazedoxifene ... CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the ...

7. aacrjournals.org aacrjournals.org/cancerpreventionresearch/article/12/10/711/47192/Effect-of-Bazedoxifene-and-Conjugated-Estrogen

Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on ... We demonstrated excellent retention and favorable change in multiple risk biomarkers for breast cancer with 6 months of Duavee in perimenopausal and ...