Topical Endoxifen in Women (CREME)

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

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.

Study Overview

• Status: Completed
• Conditions: Mammographic Breast Density
• Intervention / Treatment: Drug: Placebo; Drug: Topical endoxifen

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Sodersjukhuset
    • Stockholm, Sodersjukhuset, Sweden
      • Karolinska Institutet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Topical Placebo:Transcutol™ (2-(2-Ethoxyethoxy)ethanol); isopropanol, Crodamol™ GTCC (a fully saturated emollient triester) and mineral oil	Drug: Placebo; topical
Active Comparator: 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	Drug: Topical endoxifen; topical solution
Active Comparator: 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	Drug: Topical endoxifen; topical solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Atossa Therapeutics, Inc.
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Per Hall, MD, Karolinska Institutet

Publications and helpful links

General Publications

• Backlund M, Eriksson M, Gabrielson M, Hammarstrom M, Quay S, Bergqvist J, Hellgren R, Czene K, Hall P. Topical Endoxifen for Mammographic Density Reduction-A Randomized Controlled Trial. Oncologist. 2022 Jul 5;27(7):e597-e600. doi: 10.1093/oncolo/oyac102.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): September 10, 2018
• Study Completion (Actual): September 4, 2019

Study Registration Dates

• First Submitted: October 16, 2020
• First Submitted That Met QC Criteria: November 4, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): July 12, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: ATOS-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No