Karolinska Interventional Study of Mammograhic Density (Karisma-1) (Karisma-1)

A Randomized, Open Pilot Study to Investigate the Mammographic Density Reduction on Healthy Women, Within the Karma Cohort, for Two Different Doses of Tamoxifen

A feasibility study, randomising to either 10 or 20 mg of tamoxifen. The primary aim is to identify the time to mammographic density change and piloting the procedures. It is known that a density change is seen after 12 months of 20 mg of tamoxifen, but the clinical experience indicates that an effect of drugs influencing mammographic density could be seen already after a few months. The second aim is to evaluate if there is a density change from 10 mg of tamoxifen equivalent to 20 mg.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Mammographic Density
• Intervention / Treatment: Drug: Tamoxifen

Detailed Description

The investigators want to conduct a feasibility study including 42 women who will be randomised to either 10 or 20 mg of daily oral tamoxifen. The primary aim of the study is to identify the time to mammographic density change and piloting the procedures. It is known that a density change is seen after 12 months of 20 mg of daily tamoxifen, but the clinical experience indicates that an effect of drugs influencing mammographic density could be seen already after a few months. The second aim of the pilot study is to see if there is a density change from 10 mg of tamoxifen equivalent to 20 mg and if there is a difference in adverse reactions between the two doses. Interim analysis will be performed at 6 months, monitoring both safety and level of mammographic density change.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

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:

• Previously participated in the Karma study
• Attending the national mammography screening program, i.e. aged 40-74
• A mammogram, including a stored raw image, must have been taken within 3 weeks of baseline and start of therapy
• Having a mammographic volumetric density above the lowest 1/6, measured by Volpara
• Informed consent must be signed before any study specific assessments have been performed

Exclusion Criteria:

• Being pregnant or planning to become pregnant during the study
• Any previous or current diagnosis of breast cancer (including carcinoma in situ)
• Recalled (mammographic code 3 or above) after baseline screening mammography
• Any previous diagnosis of cancer, with the exception of non-melanoma skin cancer and in situ cancer of the cervix
• Currently using oestrogen and progesterone-based hormone replacement therapy
• Current use of hormone contraceptive with hormones, e.g. hormonal contraceptive pills, or progesterone implants. Hormonal intrauterine devices are accepted.
• A history of thromboembolic disease such as embolism, deep vein thrombosis, stroke, TIA or cardiac arrest.
• A history of immobilization, e.g. using wheelchair
• Uncontrolled diabetes defined as known untreated diabetes
• Hypertension at baseline, defined as systolic pressure higher than 140 mm Hg and diastolic higher than 90 mm Hg
• Use of drugs that interfere with CYP2D6 expression such as paroxetine, fluoxetine and bupropion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamoxifen 10mg; Randomised dose of daily oral Tamoxifen 10mg, for 180 days	Drug: Tamoxifen; A registered SERM drug, Tamoxifen.
Active Comparator: Tamoxifen 20mg; Randomised dose of daily oral Tamoxifen 20mg, for 180 days	Drug: Tamoxifen; A registered SERM drug, Tamoxifen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to mammographic density change	Mammographic density followed on repeated mammographies by measurements using STRATUS software	Mammography after 0, 3, 6, 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in density change with tamoxifen 10 mg and 20 mg	Determine any differences in density change comparing 10 mg and 20 mg of daily oral tamoxifen.	Mammography after 0, 3, 6 months
Differences in and adverse events with tamoxifen 10 mg and 20 mg	Determine any differences in adverse events comparing 10 mg and 20 mg of daily oral tamoxifen.	Questionnaires after 0, 1, 3, 6 months

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Per Hall, MD, PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 3, 2019
• First Submitted That Met QC Criteria: September 3, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): September 9, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Tamoxifen; Randomized Clinical Trial; Low-dose
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: 2015-000345; 2014-005005-20 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No