Phase 2
N=1,440
Low Dose Tamoxifen for Mammographic Density Reduction
Risk Reduction · Mammographic Density Reduction
Bottom Line
View on ClinicalTrials.gov: NCT03346200 ↗Enrolled (actual)
1,440
Serious AEs
0.8%
Results posted
Mar 2025
Primary outcome: Primary: Mammograpic Density Change — -9.6; -6.8; -1.0; -6.9 Percentage of change — p=<0.01
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tamoxifen Oral Tablet (Drug); Placebo Oral Tablet (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- Female
- Sponsor
- Per Hall
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mammograpic Density Change |
-9.6; -6.8; -1.0; -6.9; -1.0; 0.1 | <0.01 sig |
| SECONDARY Level of Side Effects |
2.71; 2.97; 2.52; 2.39; 1.65; 0.36 | — |
| SECONDARY Drop Out Level |
65; 69; 79; 71; 58; 53 | — |
Summary
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT03346200). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.