NCT03346200

Brief 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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,440

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2016

Typical duration for phase_2

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2016

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

November 1, 2017

Completed
16 days until next milestone

First Posted

Study publicly available on registry

November 17, 2017

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2019

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
5.3 years until next milestone

Results Posted

Study results publicly available

March 7, 2025

Completed
Last Updated

March 7, 2025

Status Verified

March 1, 2025

Enrollment Period

2.9 years

First QC Date

November 1, 2017

Results QC Date

March 12, 2024

Last Update Submit

March 4, 2025

Conditions

Risk ReductionMammographic Density Reduction

Keywords

Breast cancerPreventionTamoxifen

Outcome Measures

Primary Outcomes (1)

  • Mammograpic Density Change

    Change in mammography density. In particular, we will test for noninferiority in the proportion of women in the intervention arms (placebo, 1 mg, 2.5 mg, 5 mg, 10 mg) who have a density reduction as great as or greater (after 6 months) than the median density reduction in the 20 mg arm.

    6 months treatment

Secondary Outcomes (2)

  • Level of Side Effects

    From baseline (7-1days before first tablet) up to 6 months or day of discontionuation (prior to 6 months)

  • Drop Out Level

    From initiation of treatment (first tablet) up to 6 months of planned treatment (last tablet)

Study Arms (6)

20 mg tamoxifen

ACTIVE COMPARATOR
Drug: Tamoxifen Oral Tablet

10 mg tamoxifen

EXPERIMENTAL
Drug: Tamoxifen Oral Tablet

5 mg tamoxifen

EXPERIMENTAL
Drug: Tamoxifen Oral Tablet

2.5 mg tamoxifen

EXPERIMENTAL
Drug: Tamoxifen Oral Tablet

1 mg tamoxifen

EXPERIMENTAL
Drug: Tamoxifen Oral Tablet

0 mg tamoxifen

PLACEBO COMPARATOR
Drug: Placebo Oral Tablet

Interventions

Tamoxifen Oral TabletDRUG

Randomised dose of tamoxifen 1 pill/day for 180 days

1 mg tamoxifen10 mg tamoxifen2.5 mg tamoxifen20 mg tamoxifen5 mg tamoxifen
Placebo Oral TabletDRUG

Randomised dose of tamoxifen 1 pill/day for 180 days

0 mg tamoxifen

Eligibility Criteria

Age40 Years - 74 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsFemale mammography screening population in Sweden age 40-74
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (4)

  • Eriksson M, Eklund M, Borgquist S, Hellgren R, Margolin S, Thoren L, Rosendahl A, Lang K, Tapia J, Backlund M, Discacciati A, Crippa A, Gabrielson M, Hammarstrom M, Wengstrom Y, Czene K, Hall P. Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial. J Clin Oncol. 2021 Jun 10;39(17):1899-1908. doi: 10.1200/JCO.20.02598. Epub 2021 Mar 18.

    PMID: 33734864RESULT

  • Goransson S, Hernandez-Varas P, Hammarstrom M, Hellgren R, Backlund M, Lang K, Rosendahl AH, Eriksson M, Borgquist S, Stromblad S, Czene K, Hall P, Gabrielson M. Low-dose tamoxifen treatment reduces collagen organisation indicative of tissue stiffness in the normal breast: results from the KARISMA randomised controlled trial. Breast Cancer Res. 2024 Nov 26;26(1):163. doi: 10.1186/s13058-024-01919-1.

    PMID: 39593191DERIVED

  • Hammarstrom M, Gabrielson M, Crippa A, Discacciati A, Eklund M, Lundholm C, Backlund M, Wengstrom Y, Borgquist S, Bergqvist J, Eriksson M, Tapia J, Czene K, Hall P. Side effects of low-dose tamoxifen: results from a six-armed randomised controlled trial in healthy women. Br J Cancer. 2023 Jul;129(1):61-71. doi: 10.1038/s41416-023-02293-z. Epub 2023 May 6.

    PMID: 37149701DERIVED

  • Gabrielson M, Hammarstrom M, Backlund M, Bergqvist J, Lang K, Rosendahl AH, Borgquist S, Hellgren R, Czene K, Hall P. Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women. Int J Cancer. 2023 Jun 1;152(11):2362-2372. doi: 10.1002/ijc.34430. Epub 2023 Jan 22.

    PMID: 36637153DERIVED

Related Links

MeSH Terms

Conditions

Risk Reduction BehaviorBreast Neoplasms

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

BehaviorNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

StilbenesBenzylidene CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Results Point of Contact

Title
PI Professor MD Per Hall
Organization
KARMA project, Karolinska Institute
Per.hall@ki.se
+46 8 524 85000

Study Officials

  • Per Hall, Professor

    Karolinska Institutet

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor, MD, PhD

Study Record Dates

First Submitted

November 1, 2017

First Posted

November 17, 2017

Study Start

November 1, 2016

Primary Completion

October 1, 2019

Study Completion

December 1, 2019

Last Updated

March 7, 2025

Results First Posted

March 7, 2025

Record last verified: 2025-03

Data Sharing

IPD Sharing
Will not share