PharmacoKINEtics of TAMoxifen and Its Metabolites in Brea... | NCT01192308

Status Module

Record Verification Date

Nov 2020

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Jul 2010

Primary Completion Date

May 2011Actual

Completion Date

May 2012Actual

First Submitted Date

Aug 30, 2010

First Submission Date that Met QC Criteria

Aug 31, 2010

First Posted Date

Sep 1, 2010Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Nov 26, 2020

Last Update Posted Date

Dec 1, 2020Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 1

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

42Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
40mg QD dose intervention	Experimental	40mg QD dose intervention during 4 weeks in patients with CYP2D6 variant allele or using CYP2D6 inhibitor.	Drug: Tamoxifen 40mg QD

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Tamoxifen 40mg QD	Drug	Tamoxifen 40mg QD during 4 weeks	40mg QD dose intervention

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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

Other Outcomes

Not provided

Eligibility Module

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.

Accepts Healthy Volunteers

Sex

Female

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
David M Burger, PharmD, PhD	Radboud University Medical Center	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Radboud University Nijmegen Medical Centre		Nijmegen			Netherlands

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26192892	Result	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.

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D013267	Stilbenes
D001597	Benzylidene Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals