The effects of switching antidepressants on endoxifen exposure

Conditions: Breast cancer
MedDRA version: 13.1Level: LLTClassification code 10070577Term: Oestrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-002727-18-NL

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 13

Inclusion Criteria

- Histological or cytological confirmed diagnosis of 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 end of the study;
- Concomitant use of paroxetine for at least 14 days;
- Age >18 years;
- WHO performance < 1

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 13
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Pregnant or lactating patients
- Patients with a history of suicide attempts or current suicidal ideation;
- Contra-indications for venlafaxine and/or escitalopram use;
- Patients with Congenital Long QT Syndrome (CLQTS).

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 effects of switching from the potent CYP2D6 inhibitor paroxetine to a weak CYP2D6 inhibitor (venlafaxine, escitalopram) on the metabolism and plasma pharmacokinetics of tamoxifen and its metabolites in breast cancer patients on tamoxifen therapy. ;Secondary Objective: - To compare toxic adverse effects in treatment courses with tamoxifen before and after switching from a potent CYP2D6 inhibitor to a weak CYP2D6 inhibitor. <br>- To study the influence of genetic polymorphisms in enzymes involved in the metabolism of tamoxifen on the formation of endoxifen and 4-hydroxy-tamoxifen, in the presence of a potent or weak CYP2D6 inhibitor.<br>;Primary end point(s): This is a pharmacokinetic study intended to investigate the effects of switching from the potent CYP2D6 inhibitor paroxetine to a weak inhibitor of CYP2D6 on the plasma pharmacokinetics of tamoxifen and its metabolites.;Timepoint(s) of evaluation of this end point: 36 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Influence of genetic polymorphisms in CYP enzymes involved in the metabolism of tamoxifen<br>- Adverse reactions;Timepoint(s) of evaluation of this end point: 36 months