Optimizing tamoxifen therapy through the induction of CYP3A4, CYP2C and CYP2D6 mediated metabolism - Induction of tamoxifen metabolism

Conditions: Breast cancer
MedDRA version: 12.1Level: LLTClassification code 10006187Term: Breast cancer

Registration Number: EUCTR2010-023776-52-NL

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 12

Inclusion Criteria

•Histological or cytological confirmed diagnosis of (invasive) breast cancer, for which treatment with tamoxifen monotherapy is indicated (to be evaluated by the treating physician);
•Use of tamoxifen monotherapy for at least 4 weeks (to guarantee steady-state) and willing to continue the treatment until the second day of pharmacokinetic analyses;

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Pregnant or lactating patients;
•Impossibility to take oral drugs;
•Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent;
•Contra-indications for rifampicin and/or dextromethorphan use;
•Use of medications or dietary supplements known to induce or inhibit CYP2D6, CYP2C, CYP3A4 and/or P-glycoprotein;
•Unwillingness to abstain from grapefruit (juice), (herbal) dietary supplements, herbals, over-the-counter medication (except for paracetamol and ibuprofen) and other drugs known to seriously interact with CYP3A during the study period;
•Non-compliance

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: -To determine the influence of cytochrome P450 enzyme induction (including CYP3A4, CYP2C and CYP2D6) by rifampicin on the metabolism and plasma pharmacokinetics of tamoxifen and its metabolites in breast cancer patients. ;Secondary Objective: -To compare the incidence and severity of side effects of treatment with tamoxifen in the presence and absence of rifampicin. <br>-To validate the previously developed dextromethorphan phenotyping test;Primary end point(s): This is a randomized crossover pharmacokinetic study intended to investigate the effect of cytochrome P450 enzyme induction (including CYP3A4, CYP2C and CYP2D6) by rifampicin on the metabolism and plasma pharmacokinetics of tamoxifen and its metabolites.

Secondary Outcome Measures