PharmacoKINEtics of TAMoxifen and Its Metabolites in Breast Cancer Patients: the Influence of a Dose Increase in Phenotypic Poor Metabolizers of CYP2D6 (KINETAM)

Study Overview
=================
Brief Summary
-----------------
All women on tamoxifen receive the standard dose of 20mg QD, irrespective of the use of potential CYP2D6 inhibitors, and are not tested for CYP2D6 polymorphisms prior to start of tamoxifen treatment.However CYP2D6 polymorphisms and/or the use of CYP2D6 inhibitors as co-medication may influence the treatment outcome of tamoxifen. The investigators propose a prospective study in women taking tamoxifen at a dose of 20mg QD. In each woman, information will be collected on endoxifen levels, CYP2D6 status, adherence and use of co-medication. In women who are phenotypically poor metabolizers of tamoxifen, a dose increase to 40mg QD will be applied and the effect of this intervention on tamoxifen pharmacokinetics will be evaluated after 4 weeks.

Detailed Description
-----------------
Although already some information is available on the importance of CYP2D6 polymorphisms and/or the use of CYP2D6 inhibitors as co-medication that may influence the treatment outcome of tamoxifen, this information does currently not lead to a change in the management of this patient population. All women on tamoxifen receive the standard dose of 20mg QD, irrespective of the use of potential CYP2D6 inhibitors, and are not tested for CYP2D6 polymorphisms prior to start of tamoxifen treatment. In an attempt to at least resolve some of these issues we propose a prospective study in women taking tamoxifen at a dose of 20mg QD who are being followed at several large oncology clinics in the south-eastern part of the Netherlands (Nijmegen (CWZ & Radboud), Den Bosch, Harderwijk and Arnhem). In each woman, information will be collected on endoxifen levels, CYP2D6 status, adherence and use of co-medication. In women who are phenotypically poor metabolizers of tamoxifen, a dose increase to 40mg QD will be applied and the effect of this intervention on tamoxifen pharmacokinetics will be evaluated after 4 weeks.

Official Title
-----------------
PharmacoKINEtics of TAMoxifen and Its Metabolites in Breast Cancer Patients: the Influence of a Dose Increase in Phenotypic Poor Metabolizers of CYP2D6 (KINETAM)

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Tamoxifen 40mg QD


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is at least 18 years at screening. Subject is able and willing to sign the Informed Consent Form prior to screening evaluations. Subject is a female patient with (a history of) breast cancer and has been treated with tamoxifen 20mg QD for at least 4 weeks and is expected to be treated for at least another 4 weeks Exclusion Criteria: Inability to understand the nature and extent of the trial and the procedures required. Participation in a drug trial within 60 days prior to the first dose.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40mg QD dose intervention<br>40mg QD dose intervention during 4 weeks in patients with CYP2D6 variant allele or using CYP2D6 inhibitor. | Drug: Tamoxifen 40mg QD<br>* Tamoxifen 40mg QD during 4 weeks<br>* Other names: Nolvadex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tamoxifen and metabolites plasmaconcentration | Trough samples | week 0 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Collection of adverse events during entire trial. | week 0 and 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Tamoxifen, Pharmacokinetics, Pharmacogenetics, CYP2D6