Mammography Screening, Breast Density
Conditions
Keywords
Progesterone receptor modulators
Brief summary
This phase II trial tests whether taking ulipristal acetate prior to a mammogram decreases breast density for people with a history of extremely dense breast tissue. One limitation to breast cancer screening with mammography is dense breast tissue, which decreases the sensitivity of screening as breast density masks cancer and precancerous lesions. Ulipristal acetate lowers the amount of progesterone made by the body which may temporarily decrease the density of the breast tissue, allowing for a more accurate mammogram for people with extremely dense breast tissue.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate change in percent dense area from antecedent to study screening mammograms. SECONDARY OBJECTIVES: I. To assess for menstrual cycle phase following this regimen of ulipristal acetate (UPA). II. To assess adherence, tolerability and acceptability of the short course of UPA prior to a mammogram. EXPLORATORY OBJECTIVES: I. To determine the presence of radiographic changes in clinical breast density on screening mammograms following a course of UPA. II. To characterize a change in background parenchymal enhancement (BPE) on breast magnetic resonance (MR). III. To describe the effect of the intervention on routine clinical care. IV. To determine the longitudinal effect of the intervention on primary objective (clinical breast density score). OUTLINE: Patients receive ulipristal acetate orally (PO) every 5 days for 4 doses in the absence of unacceptable toxicity (study days 1, 5, 10 and 15). Patients then undergo a mammogram on study day 20. Patients also undergo base magnetic resonance imaging (MRI) and blood sampling which will be repeated on study day 20. After completion of study intervention, patients are followed up at 1-7 days and may be followed up to 24 months for results of subsequent screening mammograms.
Interventions
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDUREMammogram
Participants will undergo their standard of care mammogram.
OTHERSurvey Administration
Ancillary studies
DRUGUlipristal Acetate
Given orally
Sponsors
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Participant or legally authorized representative (LAR) must provide written informed consent before any study-specific procedures or interventions are performed * Ages 18-50 years. The maximum age cut off is due to the intervention only applying to premenopausal physiology only * Assigned female at birth with at least one ovary in situ. Members of all races and ethnic groups will be included * Presenting for a screening mammogram * Has an antecedent mammogram within 24 months with a Breast Imaging Reporting and Data System (BI-RADS) breast composition score of Category D (extremely dense) for which images are available for analysis * Report no history of breast cancer or symptoms concerning for breast cancer such as a self-palpated mass * Reasonably assumed to be premenopausal by history of regular menses. For individuals who do not menstruate (due to hysterectomy or endometrial ablation), premenopausal status will be determined clinically by the absence of symptoms of menopause including weekly hot flashes which is consistent with clinical care
Exclusion criteria
* Having a mammogram as part of a diagnostic process * Current breast implants in one or both breasts * Pregnant, less than 1 year postpartum or breastfeeding within last 6 months at the time of their antecedent mammogram or their current mammogram. This exclusion is due to known changes in mammograms during pregnancy and postpartum that would preclude comparative analyses * Using hormonal medications including estrogens or progestins * History of allergy to UPA * A history of liver disease (including but not limited to viral or autoimmune hepatitis, non-alcoholic fatty liver disease, hemochromatosis or Wilson's disease), alcoholism or a history of liver function tests such as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) greater than 3 x the upper limit of normal without known etiology * Attempting pregnancy during the study duration or a positive urine pregnancy for people at risk of pregnancy who cannot be reasonably assumed not to be pregnant at the beginning of the intervention * Use of CYP3A4 inducer or inhibitors which may alter plasma concentrations of study drug (See Appendix A for list of common drugs/herbs). Regarding recent use of CYP3A4 inducers or inhibitors, a washout period will be deemed sufficient if at least 14 days or 5 half lives of the drug have elapsed prior to initiation of the study drug, whichever is longer. Participants will be advised to abstain from CYP3A4 inducers or inhibitors during the study and will only be ineligible if unable to
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in percent dense area | From baseline mammogram to study day 20 mammogram | DEEP-Libra will be utilized to obtain the change in breast percent density value per patient between the historical baseline mammogram and mammogram following ulipristal acetate. Both images (baseline and mammogram following ulipristal acetate) will be independently analyzed with DEEP-Libra to generate the percent dense area and then the mean difference will be recorded. The mean and standard deviation of the difference in percent dense area between the baseline and mammogram following ulipristal acetate will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progesterone level | At time of baseline MRI and at study day 20 | Each participant will be categorized as being in their luteal phase, follicular phase, or as experiencing imminent ovulation at the time of both breast magnetic resonance imagings (MRI): at baseline and immediately after completion of the study drug. The frequency and proportion of participants in each category will be reported and assessed descriptively, as well as median and range, or mean and standard deviation. |
| Estradiol level | At time of baseline MRI and at study day 20 | Each participant will be categorized as being in their luteal phase, follicular phase, or as experiencing imminent ovulation at the time of both breast MRIs: at baseline and immediately after completion of the study drug. The frequency and proportion of participants in each category will be reported and assessed descriptively, as well as median and range, or mean and standard deviation. |
| Luteinizing hormone level | At time of baseline MRI and at study day 20 | Each participant will be categorized as being in their luteal phase, follicular phase, or as experiencing imminent ovulation at the time of both breast MRIs: at baseline and immediately after completion of the study drug. The frequency and proportion of participants in each category will be reported and assessed descriptively, as well as median and range, or mean and standard deviation. |
| Patient reported doses and deviations greater than 24 hours from recommended doses | Study days 1, 5, 10 and 15. | Administration of the study drug and deviations of the study drug administration greater than 24 hours will be described and utilized for determination of study population from the first dose of the study drug to the day of the mammogram following ulipristal acetate. |
| Serum ulipristal acetate drug levels | Study day 20 | Will be collected on the day of the mammogram following ulipristal acetate and presented descriptively (mean, standard deviation) and only confirm receipt of final dose of study drug. |
| Incidence of adverse events | Study days 5, 10, 15 and 20 | Responses from these symptom surveys from first dose of study drug to the day of mammogram completed following ulipristal acetate will be aggregated and a binary variable will be generated to determine whether participants ever, or never, during the study period, reported each side effect/serious adverse events assessed in the surveys. |
| Acceptability of intervention | Up to 7 days after study day 20 | The frequency and proportion of participants rating the intervention as tolerable/acceptable will be reported and assessed descriptively. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAbigail Liberty
OHSU Knight Cancer Institute
Outcome results
None listed