Study on the pharmacokinetic interaction between green tea and tamoxifen in patients with breast cancer. “the TEA study”

INTERVENTION: Trade Name: tamoxifen Pharmaceutical Form: Tablet CONDITION: Breast cancer Therapeutic area: Diseases [C] ‐ Cancer [C04] PRIMARY OUTCOME: Main Objective: To compare the Area under the curve (AUC) of endoxifen in patients with breast cancer treated with tamoxifen with and without green tea. Primary end point(s): To compare the Area under the curve (AUC) of endoxifen in patients with breast cancer treated with tamoxifen with and without green tea. Secondary Objective: 1. To compare the Area under the Curve (AUC) of tamoxifen in patients with breast cancer treated with tamoxifen with and without green tea.; 2. To compare other tamoxifen and endoxifen pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), minimal concentration (Ctrough) and time until maximum concentration (tmax) and elimination half‐life (t½)). in patients with breast cancer treated with tamoxifen with and without green tea.; 3. To evaluate the incidence and severity of side‐effects of treatment with tamoxifen in absence and presence of green tea.; Timepoint(s) of evaluation of this end point: Last visit last patient SECONDARY OUTCOME: Secondary end point(s): 1. To compare the Area under the Curve (AUC) of tamoxifen in patients with breast cancer treated with tamoxifen with and without green tea.; 2. To compare other tamoxifen and endoxifen pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax), minimal concentration (Ctrough) and time until maximum concentration (tmax) and elimination half‐life (t½)). in patients with breast cancer treated with tamoxifen with and without green tea.; 3. To evaluate the incidence and severity of side‐effects of treatment with tamoxifen in absence and presence of green tea.; Timepoint(s) of evaluation of this end point: Last visit last patient INCLUSION CRITERIA: 1. Age = 18 years 2. Patients with a confirmed diagnosis of primary or advanced breast cancer, who are on tamoxifen treatment for at least three months (steady state concentration). 3. WHO performance = 1 (see Appendix B) 4. Able and willing to sign the informed consent form prior to screening evaluations 5. Willing to abstain from strong CYP3A4, CYP2D6, CYP2C9/2C19, UGT and P‐gp inhibitors or inducers, herbal or dietary supplements or other over‐the‐counter medication besides paracetamol. (see Appendix C) 6. Adequate organ function defined as: ‐ ALAT and ASAT <5.0 upper limit of normal (ULN) ‐ bilirubin <1.5 (ULN) ‐ GFR > 30 ml/min/1.73 m2 7. Endoxifen trough concentration of 16 nM Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age r