Duavee for Breast Cancer

Recruiting at 9 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

142 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment on women with early-stage breast cancer to see if it can reduce cancer risk by changing specific signs in breast tissue.

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.

What data supports the effectiveness of the drug Duavee for breast cancer?

The research highlights that endocrine therapy, which includes drugs that affect estrogen receptors like Duavee, is a key part of treating hormone-sensitive breast cancer. While Duavee itself isn't directly mentioned, similar treatments that target estrogen receptors have been shown to reduce the risk of cancer recurrence and improve outcomes. ^{1 2 3 4 5}

Is Duavee (conjugated estrogens/bazedoxifene) safe for humans?

Research shows that Duavee, also known as conjugated estrogens/bazedoxifene, has been evaluated for safety in treating menopausal symptoms and preserving bone health. Studies indicate it has a safety profile comparable to other hormone therapies, with specific attention to cardiovascular safety and risks like endometrial and breast cancer. ^{6 7 8 9 10}

How is the drug Duavee unique for breast cancer treatment?

Duavee, a combination of conjugated estrogens and bazedoxifene, is unique because it pairs a selective estrogen receptor modulator with estrogens, potentially reducing breast cancer risk by sensitizing cancer cells to estrogen-induced cell death while also managing menopausal symptoms. ^{7 11 12 13 14}

Research Team

Swati Kulkarni, MD

Principal Investigator

Northwestern University

Eligibility Criteria

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.

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.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of breast cancer. Endocrine therapy]. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Pretreatment predictors of short-term nonadherence to oral hormonal therapy for women with breast cancer. [2021]

3. Japan pubmed.ncbi.nlm.nih.gov

[CURRENT PERSPECTIVE ON SYSTEMIC THERAPY FOR BREAST CANCER]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Endocrine therapy use among elderly hormone receptor-positive breast cancer patients enrolled in Medicare Part D. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Adherence to oral endocrine treatments in women with breast cancer: can it be improved? [2022]

6. England pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Bazedoxifene for HRT? [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Sleep parameters and health-related quality of life with bazedoxifene/conjugated estrogens: a randomized trial. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a third-generation selective estrogen receptor modulator for treatment of postmenopausal osteoporosis. [2012]

11. United States pubmed.ncbi.nlm.nih.gov

Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

A(nother) scientific strategy to prevent breast cancer in postmenopausal women by enhancing estrogen-induced apoptosis? [2021]

13. England pubmed.ncbi.nlm.nih.gov

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

14. England pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. [2012]