Pilot Study of Effects of Duavee® on Imaging and Blood Biomarkers In Women With Menopausal Symptoms

Pilot Study of Effects of Duavee® on Imaging and Blood Biomarkers In Women With Menopausal Symptoms at Increased Risk for Breast Cancer

Pilot study to test feasibility of 6 months of Duavee® vs wait-list control in post-menopausal women symptomatic for hot flashes.

Study Overview

• Status: Terminated
• Conditions: Focus of Study is Healthy Women at Risk for Breast Cancer
• Intervention / Treatment: Drug: DUAVEE 0.45Mg-20Mg Tablet

Detailed Description

Duavee® which is the combination of the selective estrogen receptor modulator bazedoxifene and conjugated estrogen 0.45 mg) is an FDA approved drug for treatment of hot-flashes and prevention of osteoporosis in postmenopausal women. The investigators recently reported the results of a single arm pilot study suggesting that 6 months of Duavee® was associated with improvement in several risk biomarkers including benign breast tissue proliferation, mammographic fibroglandular volume, IGF-1, SHBG and progesterone in high risk women in late menopause transition. Prior to opening a randomized Phase IIB trial of 6 months of Duavee® vs placebo in high risk women with hot-flashes followed by open label Duavee®, the intent of this study is to assess probable uptake of such a trial design with a pilot of 6 months of Duavee® vs wait-list control in symptomatic women. Additional imaging biomarker information from MRI will be obtained. A finding on MRI of greater background parenchymal enhancement (BPE) in high risk women is positively associated with higher probability of developing breast cancer and is independent of fibroglandular volume. BPE is reduced by selective estrogen receptor modulators including tamoxifen. The investigators will investigate change in MRI BPE over time for women randomly assigned to either receive Duavee® or not (wait-list control). The investigators will also explore development of fully automated breast MRI volumetric density measures.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160-7820
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women who report vasomotor symptoms (hot flashes or night sweats)
• No menstrual periods for at least 3 months
• Must have at least one ovary (hysterectomy is permitted; bilateral salpingo- oophorectomy is excluded).
• BMI <36 kg/m2

• Moderate risk of developing breast cancer based on having any one or more of the following:

  • First or 2nd degree relative with breast cancer
  • Known carrier of moderate to high penetrance germline mutation
  • Prior breast biopsy showing proliferative breast disease or multiple biopsies
  • High mammographic density (Volpara® categories c or d or BIRADs density assessment as heterogeneously or extremely dense (c or d).
  • IBIS Breast Cancer Risk Evaluation Version 8 10-year relative risk of >2X that for the population for age group.

Exclusion Criteria:

• Risk: A prior biopsy showing LCIS, DCIS, or invasive breast cancer.

• Medical Conditions:

  • Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke
  • History of renal or liver disease
  • Prior invasive ovarian or endometrial cancer

• Medications

  • Current anticoagulant use other than low dose aspirin
  • Taking systemic hormones within two months (eight weeks) prior to baseline MRI and mammogram.
  • Taking tamoxifen, raloxifene, Duavee, or any selective estrogen receptor modulator, or an aromatase inhibitor within 12 months prior to baseline MRI and mammogram.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Immediate active agent; Duavee. One capsule daily for 6 months (+/- 1 month) of Duavee (Bazedoxifene 20 mg plus conjugated estrogens 0.45 mg)	Drug: DUAVEE 0.45Mg-20Mg Tablet; One capsule daily for 6 months (+/- 1 month); Other Names: Bazedoxifene 20 mg plus conjugated estrogens 0.45 mg
OTHER: Delayed active agent; No intervention for first 6 months. Then option to receive daily Duavee for 6 months.	Drug: DUAVEE 0.45Mg-20Mg Tablet; One capsule daily for 6 months (+/- 1 month); Other Names: Bazedoxifene 20 mg plus conjugated estrogens 0.45 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of potential participants who consent to enrollment	Trial design is acceptable to potential subjects, as evidenced by participation	Enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in breast background parenchymal enhancement (BPE)	BPE assessed by abbreviated MRI at baseline and after 6 months	6 months
Change in fibroglandular volume (FGV)	FGV assessed by Volpara software on 3D mammograms acquired at baseline and after 6 months	6 months

Collaborators and Investigators

• Sponsor: Carol Fabian, MD
• Collaborators: Breast Cancer Research Foundation

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2020
• Primary Completion (ACTUAL): July 30, 2021
• Study Completion (ACTUAL): July 31, 2021

Study Registration Dates

• First Submitted: May 3, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (ACTUAL): May 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Imaging; Biomarkers
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: Study00145121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No