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

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

Detailed Description
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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.

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

Conditions
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Focus of Study is Healthy Women at Risk for Breast Cancer

Intervention / Treatment
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* Drug: DUAVEE 0.45Mg-20Mg Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized to active agent or wait-list control.
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imaging, Biomarkers