Pilot Study of Bazedoxifene Plus Conjugated Estrogen on Imaging and Blood Biomarkers

• Status: Not yet recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: Female

Summary

Pilot study to test feasibility of 6 months of bazedoxifene (BZA) plus conjugated estrogens (CE) to modulate breast MRI parameters.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Carol Fabian, MD
• Treatments: Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)

Criteria

Inclusion Criteria:

• Women who report vasomotor symptoms (hot flashes or night sweats or both).

• No menstrual periods for at least 60 days.

• Age 45-65. Women age 45-49 with prior hysterectomy or endometrial ablation with rare or no periods due to ablation must have a Follicle Stimulating Hormone (FSH) of 25 mIU/ml or higher to be eligible.

• BMI <36 kg/m2

• Risk Factors/Level. Moderate risk of developing breast cancer based on either by 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 prior 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 (http://www.emstrials.org/riskevaluator/). 10-year relative risk of >2X that for the population for age group.

• Prior mammogram must have at least a Volpara® fibroglandular volume of 80 cm3 or BIRADs b, c, or d category density and/or investigator estimated visual dense area of at least 25%. The entire breast must be incorporated in a single view for both the right and left breast. (i.e., women whose breasts are so large that the images must be captured as a mosaic are not eligible). If no prior mammogram, but breast density is readily appreciated and documented on physical exam, a study-provided 3D mammogram with Volpara® software must be performed to document above eligibility criterion. It will then constitute the baseline mammogram.

• Willing to comply with study procedures:

• Have blood drawn for screening tests - comprehensive metabolic panel (plus FSH if age 45-49 and no uterus or endometrial ablation)

• Have blood drawn to archive serum for assay of estradiol, testosterone, progesterone, sex hormone binding globulin (SHBG), FSH at baseline and 6-month visits (and 12 months for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months).

• Undergo a history, physical, and breast exam at baseline and 6-month visits (and 12 months for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months). History, physical exam and breast exam performed by a study-associated clinician within 3 months prior to enrollment may be substituted for baseline evaluations.

• Have a mammogram at University of Kansas Medical Center (KUMC) with Volpara® volumetric density at baseline and 6-month visits (and 12 months for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months).

• Have a study provided abbreviated MRI at KUMC at baseline and 6-month visits.

• Be contacted by the trial coordinator by phone, email, or text at months 1 and 3 (and months 7 and 9 for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months).

• Complete Mayo Clinic hot flash assessment at baseline and 6-month visits (and month 12 for women originally randomized to wait list control and subsequently taking BZA+CE for the next 6 months).

• Women 45-55 with a functional uterus (e.g., no prior endometrial ablation), menstrual period in the past 12 months, and heterosexually active, must be agreeable to use some non-hormonal form of contraception while taking BZA+CE unless husband or partner has had a vasectomy.

• Able to understand and sign an informed consent form for screening and for intervention.

• Participants on the optional random periareolar fine needle aspiration (RPFNA) procedures must meet eligibility criteria for participation on HSC4601, Breast Random Fine Needle Aspiration and/or Nipple Aspirate Fluid Collection of Breast Tissue to Aid in Short-term Risk Assessment. Participants must sign a separate optional consent for this study as well as for HSC4601. However, any eligibility criteria dealing with hormone replacement therapy and SERMs are excluded to allow the 6-month aspiration.

• Comprehensive Metabolic Panel shows clinically acceptable renal and hepatic function lab values.

• For women with intact uterus and ovary(ies) and less than age 55, a negative pregnancy test is required.

Exclusion Criteria:

• Risk: A prior biopsy showing pleomorphic lobular or ductal carcinoma in situ 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

• Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for BZA+CE.

• Medications

• Taking systemic hormones within two months (eight weeks) prior to baseline MRI and mammogram.

• 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.

Exclusion Criteria after baseline studies:

• Mammogram with Volpara® software and/or abbreviated MRI interpreted as concerning for cancer - unless recommended breast biopsy has been performed and confirmed as benign.

• Dispensing of BZA+CE for those randomized to receive it immediately does not occur within 3 months of baseline MRI.

• Unwilling to comply with future study procedures.

• Started hormone replacement, selective estrogen receptor modulator, or aromatase inhibitor after baseline studies performed but prior to randomization.