Genotype and Phenotype Guided Supplementation of TAMoxifen Standard Therapy With ENDOXifen in Breast Cancer Patients
Status:
Completed
Trial end date:
2021-05-03
Target enrollment:
Participant gender:
Summary
In hormone-receptor positive breast cancer or DCIS (ductal carcinoma in situ) tamoxifen
remains an important treatment option for patients before menopause and those patients after
menopause who cannot be treated with aromatase-inhibitors. Nonetheless, a considerable amount
of patients suffer a relapse of their cancer while on treatment with tamoxifen. Tamoxifen is
a drug that is metabolized to a variety of compounds by the human liver, and the most
important antihormonally active metabolite is called (Z)-Endoxifen. It is known that patients
who have a reduced or absent activity of the drug-metabolizing enzyme CYP2D6 have lower
levels of (Z)-Endoxifen. Furthermore, it has been observed that patients on tamoxifen therapy
who have absent CYP2D6 activity are at a 2-fold increased risk for disease recurrence, and
patients with lower CYP2D6 compared to patients with normal CYP2D6 activity still have a
1.4-fold increased risk for disease recurrence.
This trial will include patients who are already on tamoxifen therapy for at least 3 months
and is designed to show that in patients with absent or low CYP2D6 activity, (Z)-Endoxifen
supplementation - that is giving (Z)-Endoxifen in addition to tamoxifen for the study period
of 42 days - can increase blood levels of (Z)-Endoxifen to therapeutic concentrations. It is
planned to included 504 patients in this blinded, randomized trial, which will have a placebo
group (receiving no (Z)-Endoxifen) and two intervention groups that will receive 0, 1.5 or 3
mg (Z)-Endoxifen depending on their CYP2D6 genetics or their (Z)-Endoxifen levels at the
start of the study.
The trial is not designed to evaluate outcome measures (that is recurrence or survival rates)
of (Z)-Endoxifen supplementation in tamoxifen treated patients, but will document the safety
of the combined administration of tamoxifen and (Z)-Endoxifen.
Phase:
Phase 2
Details
Lead Sponsor:
Robert Bosch Gesellschaft für Medizinische Forschung mbH