Mammographic Breast Density
Conditions
Brief summary
Karma CREME-1 consisted of 90 participants from the Karma Cohort. The major focus of the pilot trial was to estimate time to mammographic density change. The primary objective was to determine the effect size of the breast density change between topical placebo and two doses of topical endoxifen.
Interventions
DRUGTopical endoxifen
topical solution
DRUGPlacebo
topical
Sponsors
Karolinska Institutet
Atossa Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 74 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant in the Karma Cohort * Attending the national mammography screening program, i.e., aged 40-74 and have performed a screening mammogram maximum 3 months prior to study inclusion * Mammographic density \ 4.5 % density (volumetric) measured by Volpara, at the screening mammogram performed in connection to baseline (maximum 3 months prior to inclusion). The threshold value of 4.5% corresponds to the clinical Bl-RADS score A * Postmenopausal, defined as no period of menstruation during last 12 months independent of any hormonal treatment * Informed consent must be signed before any study specific assessments are performed
Exclusion criteria
* Any previous or current diagnosis of breast cancer (including carcinoma in situ). * Any previous diagnosis of cancer with the exception of non-melanoma skin cancer and in situ cancer of the cervix. * A history of major surgery of the breast, e.g., reduction or enlargement, which might affect density measurements. * Mammographic Bl-RADS malignancy code 3, or above, at baseline mammography, or at mammography during time of treatment. Recall for additional examinations due to technical problems with the mammogram is accepted. * Currently using estrogen and progesterone based hormone replacement therapy (oral or patches). Local estrogen treatment is accepted (ex. Vagifem). * Non-medical approved drugs against hot-flashes including phytoestrogen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mammographic Breast Density At Study Exit | From baseline to study exit up to 6 months | Change, on an individual level, in mammographic breast density, measured at 6 months or when exiting from the study (baseline screening mammography) |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Topical Placebo:Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil
Placebo: topical | 30 |
| Topical Endoxifen 10mg/Breast/Day 10 mg/day topical (Z)-endoxifen; Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil
Topical endoxifen: topical solution | 30 |
| Topical Endoxifen 20mg/Breast/Day 20 mg/day topical (Z)-endoxifen; Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil
Topical endoxifen: topical solution | 30 |
| Total | 90 |
Baseline characteristics
| Characteristic | Total | Topical Endoxifen 10mg/Breast/Day | Topical Endoxifen 20mg/Breast/Day | Control |
|---|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 7.5 | 56.9 years STANDARD_DEVIATION 7.97 | 57.7 years STANDARD_DEVIATION 8.41 | 54.9 years STANDARD_DEVIATION 6.01 |
| Blood pressure (diastolic) | 77.4 mm Hg STANDARD_DEVIATION 7.4 | 79.7 mm Hg STANDARD_DEVIATION 5.86 | 77.0 mm Hg STANDARD_DEVIATION 7.13 | 77.0 mm Hg STANDARD_DEVIATION 7.13 |
| Blood pressure (systolic) | 120.5 mm Hg STANDARD_DEVIATION 10.5 | 123.7 mm Hg STANDARD_DEVIATION 8.45 | 120.4 mm Hg STANDARD_DEVIATION 10.1 | 117.5 mm Hg STANDARD_DEVIATION 12.1 |
| BMI | 25.2 kg/m^2 STANDARD_DEVIATION 3.1 | 25.6 kg/m^2 STANDARD_DEVIATION 3.57 | 25.2 kg/m^2 STANDARD_DEVIATION 3.08 | 24.9 kg/m^2 STANDARD_DEVIATION 2.77 |
| Height | 166.3 cm STANDARD_DEVIATION 5.9 | 165.3 cm STANDARD_DEVIATION 6.38 | 167.0 cm STANDARD_DEVIATION 6.06 | 166.6 cm STANDARD_DEVIATION 5.14 |
| Mammographic Breast Density | 24.6 % Dense Tissue STANDARD_DEVIATION 16 | 23.9 % Dense Tissue STANDARD_DEVIATION 12.9 | 26.2 % Dense Tissue STANDARD_DEVIATION 18 | 23.6 % Dense Tissue STANDARD_DEVIATION 17.2 |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Region of Enrollment Sweden | 90 Participants | 30 Participants | 30 Participants | 30 Participants |
| Sex: Female, Male Female | 90 Participants | 30 Participants | 30 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Weight | 69.7 kg STANDARD_DEVIATION 8.8 | 69.8 kg STANDARD_DEVIATION 9.74 | 70.2 kg STANDARD_DEVIATION 9.31 | 69.0 kg STANDARD_DEVIATION 7.33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 27 / 30 | 28 / 30 | 27 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Change in Mammographic Breast Density At Study Exit
Change, on an individual level, in mammographic breast density, measured at 6 months or when exiting from the study (baseline screening mammography)
Time frame: From baseline to study exit up to 6 months
Population: Due to dropouts, analysis could only be performed 1 time at study exit. Participants were encouraged to have a mammogram at study exit; not all did.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Change in Mammographic Breast Density At Study Exit | -1.85 percent change from baseline | Standard Deviation 5.58 |
| Topical Endoxifen 10mg/Breast/Day | Change in Mammographic Breast Density At Study Exit | -2.14 percent change from baseline | Standard Deviation 6.5 |
| Topical Endoxifen 20mg/Breast/Day | Change in Mammographic Breast Density At Study Exit | -3.75 percent change from baseline | Standard Deviation 7.81 |