- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03346200
Karma Intervention Study (Karisma 2)
February 25, 2020 updated by: Per Hall
A Randomised, Double Blinded, Six-armed Placebo Controlled Study to Investigate Optimal Dose of Tamoxifen With the Most Favourable Side Effect Spectre and With Mammography Density Reduction Non-inferior to That of 20 mg Tamoxifen (Karisma 2)
This is a dose determination study aiming to identify the optimal tamoxifen dose for reducing the risk of breast cancer.
Instead of following a very large number of women, for many years, treated with different doses of tamoxifen and see if they develop breast cancer, the investigators will include 1,440 healthy women participating in the mammographic screening program at two Mammography units (Unilabs mammography, Lund and Södersjukhuset Breast Centre, Stockholm) and measure their change in mammographic density.
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.
In summary Karisma 2 will be a randomized, double-blinded, six-armed placebo controlled study to identify the dose of tamoxifen with the most favourable side effect spectra and with a density reduction non-inferior to 20 mg tamoxifen.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
1440
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 74 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Description
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
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 20 mg tamoxifen
|
Randomised dose of tamoxifen 1 pill/day for 180 days
|
Experimental: 10 mg tamoxifen
|
Randomised dose of tamoxifen 1 pill/day for 180 days
|
Experimental: 5 mg tamoxifen
|
Randomised dose of tamoxifen 1 pill/day for 180 days
|
Experimental: 2.5 mg tamoxifen
|
Randomised dose of tamoxifen 1 pill/day for 180 days
|
Experimental: 1 mg tamoxifen
|
Randomised dose of tamoxifen 1 pill/day for 180 days
|
Placebo Comparator: 0 mg tamoxifen
|
Randomised dose of tamoxifen 1 pill/day for 180 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mammograpic density change
Time Frame: 6 months treatment
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Level of side effects
Time Frame: During time of treatment (6 months)
|
Assess the level of side effects in the intervention arms compared to the 20 mg arm
|
During time of treatment (6 months)
|
Drop out level
Time Frame: During time of treatment (6 months)
|
Assess the level of drop out in the intervention arms compared to the 20 mg arm
|
During time of treatment (6 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2016
Primary Completion (Actual)
October 1, 2019
Study Completion (Actual)
December 1, 2019
Study Registration Dates
First Submitted
November 1, 2017
First Submitted That Met QC Criteria
November 14, 2017
First Posted (Actual)
November 17, 2017
Study Record Updates
Last Update Posted (Actual)
February 26, 2020
Last Update Submitted That Met QC Criteria
February 25, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-000882-22
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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