The KARISMA trials are interventional trials exploring new alternatives for primary prevention of breast cancer.
The aim of the KARISMA Endoxifen trial is to compare two different doses of Z-endoxifen with placebo, regarding effect on mammographic density and side effects. Tamoxifen has been used to prevent breast cancer recurrence in patients for >30 years. Healthy women who take tamoxifen 20 mg daily for 5 years get a 30-40% reduced risk of breast cancer, but the medication may cause side effects.
Tamoxifen is acting as a pro-drug needing to be metabolized in the liver to more active substances, via the CYP2D6 enzyme system. Endoxifen, 1 of 22 known tamoxifen metabolites, is regarded the most potent estrogen receptor inhibitor. Results from our Karma CREME study (see https://karmastudy.org/, under Recent news) and other pilot studies together with preclinical data supports the idea that Z-endoxifen has a potential to be protective against breast cancer, but with fewer side effects than tamoxifen. I would also be easier to monitor in patients, compared to tamoxifen, since no activation in the liver is necessary.
Since December 2021 we are recruiting healthy volunteers to KARISMA Endoxifen from the screening programs at the South General Hospital, St Göran’s Hospital and Karolinska Univeristy Hospital (from August 2022) in Stockholm. All women aged 40-55 years, attending the national mammography screening program, are invited. After informed consent participants are randomized to 1 or 2 mg of endoxifen or placebo.
Outcome is change in mammographic density and side effects after 6 months of treatment. A decrease in mammographic density is a proxy for a reduced risk of developing breast cancer. We are planning to recruit 240 women and it is estimated that the last inclusion will be done during 2023. You can follow the study progress on https://clinicaltrials.gov/ct2/show/NCT05068388
The KARISMA trials are interventional trials exploring new alternatives for primary prevention of breast cancer.
The aim of the KARISMA Endoxifen trial is to compare two different doses of Z-endoxifen with placebo, regarding effect on mammographic density and side effects. Tamoxifen has been used to prevent breast cancer recurrence in patients for >30 years. Healthy women who take tamoxifen 20 mg daily for 5 years get a 30-40% reduced risk of breast cancer, but the medication may cause side effects.
Tamoxifen is acting as a pro-drug needing to be metabolized in the liver to more active substances, via the CYP2D6 enzyme system. Endoxifen, 1 of 22 known tamoxifen metabolites, is regarded the most potent estrogen receptor inhibitor. Results from our Karma CREME study (see https://karmastudy.org/, under Recent news) and other pilot studies together with preclinical data supports the idea that Z-endoxifen has a potential to be protective against breast cancer, but with fewer side effects than tamoxifen. I would also be easier to monitor in patients, compared to tamoxifen, since no activation in the liver is necessary.
Since December 2021 we are recruiting healthy volunteers to KARISMA Endoxifen from the screening programs at the South General Hospital, St Göran’s Hospital and Karolinska Univeristy Hospital (from August 2022) in Stockholm. All women aged 40-55 years, attending the national mammography screening program, are invited. After informed consent participants are randomized to 1 or 2 mg of endoxifen or placebo.
Outcome is change in mammographic density and side effects after 6 months of treatment. A decrease in mammographic density is a proxy for a reduced risk of developing breast cancer. We are planning to recruit 240 women and it is estimated that the last inclusion will be done during 2023. You can follow the study progress on https://clinicaltrials.gov/ct2/show/NCT05068388