Breast Cancer
Conditions
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.
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
Interventions
DRUGDuavee
Once daily tablet of Duavee (Bazedoxifene (20 mg) plus conjugated estrogen (0.45 mg))
Sponsors
Pfizer
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 61 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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% |
| 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. |
| Change in Body Composition (Total Mass) | Change from Baseline to Month 6 | Assessment by Dual Energy X-ray Absorptivity (DEXA) |
| Levels of Bazedoxifene in the Blood | Month 6 | Assessment of concentration of bazedoxifene in plasma by High-performance liquid chromatography (HPLC) |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Duavee 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)) | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Duavee |
|---|---|
| Age, Continuous | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Fibroglandular Volume (FGV) | 133 cm-squared |
| Proliferation Index (percent of breast epithelial cells that are Ki-67 immunocytochemistry positive) | 1 percent |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 0 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
Primary
Feasibility for a Larger Trial
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
Population: potential subjects screened for eligibility.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duavee | Feasibility for a Larger Trial | Screened | 42 Participants |
| Duavee | Feasibility for a Larger Trial | Eligible | 28 Participants |
| Duavee | Feasibility for a Larger Trial | Complete | 28 Participants |
Secondary
Change in Body Composition (Total Mass)
Assessment by Dual Energy X-ray Absorptivity (DEXA)
Time frame: Change from Baseline to Month 6
Population: All subjects enrolled and completed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duavee | Change in Body Composition (Total Mass) | 0.9 kg |
Comparison: Test for within-group change using paired two-sample non-parametric etstp-value: 0.088Wilcoxon (Mann-Whitney)
Secondary
Change in Fibroglandular Volume (FGV)
Assessment of mammograms for percent of breast defined as FGV by Volpara automated assessment.
Time frame: Change from Baseline to Month 6
Population: Subjects with baseline and post-intervention mammograms assessed by Volpara
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duavee | Change in Fibroglandular Volume (FGV) | -12 cm-squared |
Comparison: Test for within-group change via paired, two-sample non-parametric testp-value: 0.043Wilcoxon (Mann-Whitney)
Secondary
Change in Ki-67
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
Population: All subjects with baseline Ki-67 \>1%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duavee | Change in Ki-67 | -1.2 change in percent positivity |
Comparison: Test for within-group change by paired two-sample non-parametric testp-value: 0.017Wilcoxon (Mann-Whitney)
Secondary
Levels of Bazedoxifene in the Blood
Assessment of concentration of bazedoxifene in plasma by High-performance liquid chromatography (HPLC)
Time frame: Month 6
Population: With residual plasma available for analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Duavee | Levels of Bazedoxifene in the Blood | 1.83 ng/ml |