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

NCT ID: NCT01192308

Last Updated: 2020-12-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2012-05-31

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.

Conditions

Breast Cancer

Keywords

Breast cancer; Tamoxifen; Pharmacokinetics; Pharmacogenetics; CYP2D6

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

40mg QD dose intervention

40mg QD dose intervention during 4 weeks in patients with CYP2D6 variant allele or using CYP2D6 inhibitor.

Group Type: EXPERIMENTAL

Tamoxifen 40mg QD

Intervention Type: DRUG

Tamoxifen 40mg QD during 4 weeks

Interventions

Tamoxifen 40mg QD

Tamoxifen 40mg QD during 4 weeks

Intervention Type: DRUG

Other Intervention Names

Nolvadex

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David M Burger, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Countries

Netherlands

References

Welzen ME, Dezentje 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/FTD.0000000000000195.

Reference Type: RESULT

PMID: 26192892 (View on PubMed)

Other Identifiers

KINETAM

Identifier Type: -

Identifier Source: org_study_id