Low Dose Tamoxifen for Mammographic Density Reduction (KARISMA2)

Per Hall

Status and phase: Completed; Phase 2

Conditions: Mammographic Density Reduction; Risk Reduction

Treatments: Drug: Tamoxifen Oral Tablet; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT03346200

2016-000882-22

Details and patient eligibility

About

KARISMA2 is a randomized, double-blinded, six-armed placebo controlled study to identify a low dose of tamoxifen, with less side-effects and a density reduction non-inferior to the standard dose of 20 mg.

Full description

This is a dose determination study aiming to identify the optimal tamoxifen dose for reducing the risk of breast cancer. The change in mammographic density is a very good marker of therapy response. Investigators will test if 1 mg, 2.5 mg, 5 mg and 10 mg reduce the mammographic density to the same extent as 20 mg.

1440 healthy women 40-74 yrs were included when adhering the national Swedish mammography screening program between 2016- 2019. Women were randomized and treated daily for 6 months. Mammograms were taken at baseline and at end of treatment and side effects were measured throughout the study trough schedueled questionnaires and spontaneous AE-reporting.

Enrollment: 1,440 patients

Sex: Female

Ages: 40 to 74 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Attending the national mammography screening program, i.e. aged 40-74 and has performed a screening mammogram maximum 3 months prior to study inclusion
• Having a measurable mammographic density, i.e. ≥4.5 % density (volumetric) measured by Volpara
• Informed consent must be signed before any study specific assessments have been performed

Exclusion criteria

• Pregnancy at start, during time of study medication and up to 3 months after quitting study medication
• Breast feeding at start, during time of study medication and up to 3 months after quitting study medication
• Any previous or current diagnosis of breast cancer (including carcinoma in situ)
• Mammographic BI-RADS code 3 or above at baseline mammography, or at a diagnostic mammography during time of treatment (the first 6 months of the study)
• Any previous diagnosis of cancer with the exception of non-melanoma skin cancer and in situ cancer of the cervix
• Currently using oral 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 thrombo-embolic disease such as embolies, deep vein thrombosis, stroke, TIA or cardiac arrest.
• Known APC (Activated protein C )- resistance, an inherited hemostatic disorder
• A history of major surgery of the breast, e.g. reduction or enlargement, which might affect density measurements
• Women who have an increased risk of venous thrombosis due to immobilization, e.g. using wheelchair
• Known uncontrolled 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 Seroxat (paroxetine), Fontex (fluoxetin) and Zyban / Voxra (bupropion)
• Use of Waran (warfarin)
• Non-medical approved drugs against hot-flashes including phytooestrogen
• Not able to understand study information and/or informed consent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,440 participants in 6 patient groups, including a placebo group

20 mg tamoxifen

Active Comparator group

Treatment:

Drug: Tamoxifen Oral Tablet

10 mg tamoxifen

Experimental group

Treatment:

Drug: Tamoxifen Oral Tablet

5 mg tamoxifen

Experimental group

Treatment:

Drug: Tamoxifen Oral Tablet

2.5 mg tamoxifen

Experimental group

Treatment:

Drug: Tamoxifen Oral Tablet

1 mg tamoxifen

Experimental group

Treatment:

Drug: Tamoxifen Oral Tablet

0 mg tamoxifen

Placebo Comparator group

Treatment:

Drug: Placebo Oral Tablet