Pilot Study of the Effect of Duavee® on Benign Breast Tissue Proliferation

• ClinicalTrials.gov Identifier: NCT02729701
• Recruitment Status: Active, not recruiting
• First Posted: April 6, 2016
• Last Update Posted: February 6, 2019
• Sponsor: University of Kansas Medical Center
• Collaborator: Pfizer
• Information provided by (Responsible Party): Carol Fabian, MD, University of Kansas Medical Center

Study Description

Brief Summary:

The purpose of this study is to learn whether daily use of Duavee® is accepted and tolerated by peri- and post-menopausal women at moderate risk for development of breast cancer.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Duavee	Phase 2

Detailed Description:

Duavee® is tissue specific estrogen complex of bazedoxifene plus conjugated estrogen which is FDA approved for relief of menopausal symptoms and prevention of osteoporosis in women with a uterus who have not been diagnosed with estrogen dependent neoplasia. The overall purpose of this research is to demonstrate in a preliminary fashion that despite reduction in menopausal symptoms, (Duavee®) does not increase and may decrease proliferation in benign breast tissue in a cohort of peri- or post-menopausal women at moderately increased risk for breast cancer. If this pilot shows rapid accrual, good retention, and lack of significant increase in the risk biomarker Ki-67 in benign breast tissue, a larger prevention trial is envisioned

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Pilot Study of the Effect of Duavee® on Benign Breast Tissue Proliferation in Peri or Post-menopausal Women at Moderate Risk for Development of Breast Cancer
• Study Start Date: April 2016
• Estimated Primary Completion Date: June 2019
• Estimated Study Completion Date: June 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Duavee; Participants will be asked to take Duavee for 6 months while on the study.	Drug: Duavee; Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg)); Other Name: conjugated estrogens/bazedoxifene

Outcome Measures

Primary Outcome Measures :

1. Feasibility for a larger trial [ Time Frame: 6 Months ]
   Outcome will be based on three separate factors used collectively to determine feasibility of the study and consideration of a subsequent larger trial. These are accrual rate (ability to accrue target number of subjects in a timely manner), dropout rate (frequency of subjects who are compliant and complete the intervention) and change in Ki-67 (increase vs decrease in percent of cells stained positive in the majority of subjects). Should accrual be inadequate or too slow; or if retention is too low; then a decision would be made not to proceed to a larger trial. Also, if there is evidence of an increase in proliferation (Ki-67) then no further studies would be planned.

Secondary Outcome Measures :

1. Change in Ki-67 [ Time Frame: Change from Baseline to Month 6 ]
   Assessment by immunocytochemistry of the percent of breast epithelial cells staining positive.
2. Change in benign breast tissue estrogen responsive genes [ Time Frame: Change from Baseline to Month 6 ]
   Assessment by RT-qPCR of breast epithelial cells of relative rate of gene expression.
3. Change in hormone levels [ Time Frame: Change from Baseline to Month 6 ]
   Assessment of concentrations of hormones in serum by radioimmunoassay
4. Change in levels of Duavee in the blood [ Time Frame: Change from Baseline to Month 6 ]
   Assessment of concentration of Duavee and metabolites in plasma
5. Change in body composition [ Time Frame: Change from Baseline to Month 6 ]
   Assessment by Dual Energy X-ray Absorptivity (DEXA)
6. Change in breast density [ Time Frame: Change from Baseline to Month 6 ]
   Assessment of mammograms for percent of breast considered to be at increased density

Eligibility Criteria

• Ages Eligible for Study: up to 61 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Women with vasomotor symptoms with a uterus who are postmenopausal or in late menopause transition
• Body Mass Index (BMI) <36 kg/m2
• Class I-III mammogram within 6 months of Random Periareolar Fine Needle Aspiration (RPFNA); If Class 0 or 4, must be resolved with additional procedures
• If previously on oral contraceptives or hormone replacement, off for 8 weeks or more prior to baseline RPFNA; the exception is low dose vaginal hormones
• Confirmed moderate risk of developing breast cancer
• RPFNA results within study defined range
• Kidney and liver function within study defined range
• Willing and able to comply with study related procedures

Exclusion Criteria:

• Previous biopsy showing evidence of breast cancer
• Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke
• History of renal or liver disease
• Prior ovarian or endometrial cancer
• Stopped or started hormone replacement within 8 weeks
• Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA
• Currently taking or have taken specific medications in the past 6 months
• Participation on any chemoprevention trial within 6 months
• Current illness which would make potential participant unsuitable for enrollment

Contacts and Locations

Locations

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

University of Kansas Medical Center Breast Cancer Prevention Center

Westwood, Kansas, United States, 66208

Sponsors and Collaborators

University of Kansas Medical Center

Pfizer

Investigators

• Principal Investigator: Carol Fabian, MD; University of Kansas Medical Center

More Information

• Responsible Party: Carol Fabian, MD, Professor, Director Breast Cancer Prevention Center, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT02729701
• Other Study ID Numbers: STUDY00002440
• First Posted: April 6, 2016
• Last Update Posted: February 6, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Results will be published in aggregate; no individual participant data will be made available.

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP); Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Hormone Antagonists; Bone Density Conservation Agents