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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen 40mg QD

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40mg QD dose intervention; 40mg QD dose intervention during 4 weeks in patients with CYP2D6 variant allele or using CYP2D6 inhibitor.	Drug: Tamoxifen 40mg QD; Tamoxifen 40mg QD during 4 weeks; 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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: David M Burger, PharmD, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• 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/FTD.0000000000000195.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: August 31, 2010
• First Posted (Estimate): September 1, 2010

Study Record Updates

• Last Update Posted (Actual): December 1, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Tamoxifen; Breast cancer; Pharmacogenetics; CYP2D6
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: KINETAM