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

Breast Cancer Clinical Trial

— KINETAM  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01192308
• Other study ID #: KINETAM
• Status: Completed
• Phase: Phase 1
• Start date: July 2010
• Est. completion date: May 2012

Study information

• Verified date: November 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 2012
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Tamoxifen 40mg QD
Tamoxifen 40mg QD during 4 weeks

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Welzen ME, Dezentjé VO, van Schaik RH, Colbers AP, Guchelaar HJ, van Erp NP, den Hartigh J, Burger DM, van Laarhoven HW. The Effect of Tamoxifen Dose Increment in Patients With Impaired CYP2D6 Activity. Ther Drug Monit. 2015 Aug;37(4):501-7. doi: 10.1097/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tamoxifen and metabolites plasmaconcentration	Trough samples	week 0 and 4
Secondary	Adverse events	Collection of adverse events during entire trial.	week 0 and 4