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

• Sponsor: University of Kansas Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02729701
• Collaborator: Pfizer (Industry)
• Enrollment: 28
• Locations: 2
• Arm: 1
• Actual Duration (Months): 37
• Patients Per Site: 14
• Patients Per Site Per Month: 0.4

Study Details

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
• 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
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Jun 1, 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 Names: conjugated estrogens/bazedoxifene

Outcome Measures

Primary Outcome Measures

1. Feasibility for a Larger Trial [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 [Change from Baseline to Month 6]

   Assessment by immunocytochemistry of the percent of breast epithelial cells staining positive. Per protocol, restricted to those subjects with baseline Ki-67 positivity >1.0% but < 4%

2. Change in Fibroglandular Volume (FGV) [Change from Baseline to Month 6]

   Assessment of mammograms for percent of breast defined as FGV by Volpara automated assessment.

3. Change in Body Composition (Total Mass) [Change from Baseline to Month 6]

   Assessment by Dual Energy X-ray Absorptivity (DEXA)

4. Levels of Bazedoxifene in the Blood [Month 6]

   Assessment of concentration of bazedoxifene in plasma by High-performance liquid chromatography (HPLC)

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 61 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
2	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 7, 2016

More Information

Publications

None provided.

• 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: Apr 6, 2016
• Last Update Posted: Mar 9, 2022
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Breast Neoplasms; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)

Study Results

Participant Flow

Recruitment Details	Women were recruited from the Breast Cancer Prevention Center. Accrual May 2016 - August 2018. 42 women were considered medically eligible and were screened by Random Periareolar Fine Needle Aspiration (RPFNA). 14 did not enter the trial for a variety of reasons.

Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Duavee
Arm/Group Description	Participants will be asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Overall Participants	28
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	28 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	27 96.4%
Unknown or Not Reported	1 3.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.6%
White	27 96.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%
Proliferation Index (percent of breast epithelial cells that are Ki-67 immunocytochemistry positive) (percent) [Median (Full Range) ]
Median (Full Range) [percent]	1
Fibroglandular Volume (FGV) (cm-squared) [Median (Full Range) ]
Median (Full Range) [cm-squared]	133

Outcome Measures

1. Primary Outcome

Title	Feasibility for a Larger Trial
Description	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.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

potential subjects screened for eligibility.

Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Measure Participants	42
Screened	42 150%
Eligible	28 100%
Complete	28 100%

2. Secondary Outcome

Title	Change in Ki-67
Description	Assessment by immunocytochemistry of the percent of breast epithelial cells staining positive. Per protocol, restricted to those subjects with baseline Ki-67 positivity >1.0% but < 4%
Time Frame	Change from Baseline to Month 6

Outcome Measure Data

Analysis Population Description

All subjects with baseline Ki-67 >1%

Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Measure Participants	15
Median (Full Range) [change in percent positivity]	-1.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duavee
	Comments	Test for within-group change by paired two-sample non-parametric test
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments	a priori threshold for statistical significance <0.05
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Change in Fibroglandular Volume (FGV)
Description	Assessment of mammograms for percent of breast defined as FGV by Volpara automated assessment.
Time Frame	Change from Baseline to Month 6

Outcome Measure Data

Analysis Population Description

Subjects with baseline and post-intervention mammograms assessed by Volpara

Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Measure Participants	26
Median (Full Range) [cm-squared]	-12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duavee
	Comments	Test for within-group change via paired, two-sample non-parametric test
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	a priori threshold for statistical significance <0.05
	Method	Wilcoxon (Mann-Whitney)
	Comments	2-sided

4. Secondary Outcome

Title	Change in Body Composition (Total Mass)
Description	Assessment by Dual Energy X-ray Absorptivity (DEXA)
Time Frame	Change from Baseline to Month 6

Outcome Measure Data

Analysis Population Description

All subjects enrolled and completed

Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Measure Participants	28
Median (Full Range) [kg]	0.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Duavee
	Comments	Test for within-group change using paired two-sample non-parametric etst
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.088
	Comments	a priori threshold for statistical significance < 0.05
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Levels of Bazedoxifene in the Blood
Description	Assessment of concentration of bazedoxifene in plasma by High-performance liquid chromatography (HPLC)
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

With residual plasma available for analysis

Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Measure Participants	25
Median (Full Range) [ng/ml]	1.83

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Self-reported adverse events
Arm/Group Title	Duavee
Arm/Group Description	Participants asked to take Duavee for 6 months while on the study. Duavee: Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
All Cause Mortality
	Duavee
	Affected / at Risk (%)	# Events
Total	0/28 (0%)
Serious Adverse Events
	Duavee
	Affected / at Risk (%)	# Events
Total	0/28 (0%)
Other (Not Including Serious) Adverse Events
	Duavee
	Affected / at Risk (%)	# Events
Total	0/28 (0%)

Limitations/Caveats

Pfizer, Inc. provided the study agent Duavee but was otherwise not involved in the design, conduct, or analysis of the trial.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.