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

Sponsor

Carol Fabian, MD (Other)

Overall Status

Terminated

CT.gov ID

NCT04379024

Collaborator

Breast Cancer Research Foundation (Other)

Enrollment

Location

Arms

Actual Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Focus of Study is Healthy Women at Risk for Breast Cancer	Drug: DUAVEE 0.45Mg-20Mg Tablet	Early Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized to active agent or wait-list control.Randomized to active agent or wait-list control.

Masking:

None (Open Label)

Masking Description:

Randomization assignment is masked to all roles prior to randomization. Subsequent to randomization, agent is dispensed open-label.

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 1, 2020

Actual Primary Completion Date :

Jul 30, 2021

Actual Study Completion Date :

Jul 31, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Number of potential participants who consent to enrollment [Enrollment]
Trial design is acceptable to potential subjects, as evidenced by participation

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.