NCT03931928

Genotype and Phenotype Guided Supplementation of TAMoxifen Standard Therapy With ENDOXifen in Breast Cancer Patients

Genotype and Phenotype Guided Supplementation of TAMoxifen Standard Therapy With ENDOXifen in Breast Cancer Patients (TAMENDOX)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 356 (actual)
• Sponsor: Robert Bosch Gesellschaft für Medizinische Forschung mbH (RBMF) · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Breast Cancer
• DCIS

Interventions

Type	Name	Description
DRUG	(Z)-Endoxifen supplementation according to genotype	Group 2: CYP2D6 genotype predicted intermediate metabolizer receive 1.5 mg, poor metabolizer receive 3 mg (Z)-Endoxifen and extensive or ultrarapid metabolizer receive 0 mg endoxifen (Placebo)
DRUG	(Z)-Endoxifen supplementation according to plasma levels	Group 3: Patients will receive (Z)-endoxifen according to (Z)-endoxifen steady state plasma concentrations (phenotype) at screening (i.e. ≤ 15 nM receive 3 mg, \> 15 and ≤ 25 nM receive 1.5 mg (Z)-Endoxifen and \> 25 nM receive 0 mg (Placebo)

Timeline

• Start date: 2019-09-10
• Primary completion: 2021-05-03
• Completion: 2021-05-03
• First posted: 2019-04-30
• Last updated: 2021-09-17

Locations

40 sites across 1 country: Germany