Topical Endoxifen in Women

Study Overview
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Brief Summary
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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.

Official Title
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Karma CREME-1: A Double-blind, Placebo-controlled, Three-armed, Pilot Study of the Effects, Safety and Tolerability of Topical Endoxifen in Women Within the Karma Cohort

Conditions
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Mammographic Breast Density

Intervention / Treatment
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* Drug: Topical endoxifen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Topical Placebo:Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil | Drug: Placebo<br>* topical<br>|
| Active Comparator: Topical Endoxifen 10mg/breast/day<br>10 mg/day topical (Z)-endoxifen; Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil | Drug: Topical endoxifen<br>* topical solution<br>|
| Active Comparator: Topical Endoxifen 20mg/breast/day<br>20 mg/day topical (Z)-endoxifen; Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil | Drug: Topical endoxifen<br>* topical solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | From baseline to study exit up to 6 months |