Clinical trial NCT04379024: Pilot Study of Effects of Duavee® on Imaging and Blood Biomarkers In Women With Menopausal Symptoms
Official title: Pilot Study of Effects of Duavee® on Imaging and Blood Biomarkers In Women With Menopausal Symptoms at Increased Risk for Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Focus of Study is Healthy Women at Risk for Breast Cancer
Keywords: Imaging
Biomarkers
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: Breast Cancer Research Foundation
First posted: 2020-05-07
Enrollment: 11
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized to active agent or wait-list control.
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of potential participants who consent to enrollment
timeFrame: Enrollment
Secondary outcomes:
measure: Change in breast background parenchymal enhancement (BPE)
timeFrame: 6 months
measure: Change in fibroglandular volume (FGV)
timeFrame: 6 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Carol J Fabian, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.