Study of Tamoxifen Dose Escalation in Breast Cancer Patients With CYP2D6 Polymorphisms

NCT ID: NCT01075802

Last Updated: 2013-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-12-31

Brief Summary

Tamoxifen is an important drug for the treatment of breast cancer. Used adjuvantly after operation in early breast cancer, tamoxifen reduces annual recurrence rate by half and cancer death by one third. Used preventatively it also reduces the risk of breast cancer by 50% in women at high risk for developing the disease Tamoxifen needs to be activated in the body to an active form called endoxifen, mainly by the enzyme called CYP2D6. Patients have variable capability to activate tamoxifen due to variable function of this enzyme. Studies showed clear correlation of specific genetic variant of CYP2D6 with endoxifen blood levels. It is estimated that up to 25% Caucasian population have reduced or even absent CYP2D6 function. More recently, there were studies that showed the correlation with genetic variant of CYP2D6 and breast cancer relapse in early breast cancer patients treated with tamoxifen. Food and Drug Authority (FDA) in America and recommended checking CYP2D6 genotype in patients receiving tamoxifen treatment, but they did not specify how to interpret the genotype results and what kind actions to take in patient with adverse genotype. The aim of the investigators study is to see if increasing tamoxifen in patients with genetic polymorphism of CYP2D6 will increase endoxifen level to the same range of most patients who have wild type (normal functional)CYP2D6.

Conditions

Breast Cancer; CYP2D6 Polymorphism

Study Design

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

Study Groups

Tamoxifen

Dose escalation of tamoxifen in patients with low endoxifen levels

Group Type: EXPERIMENTAL

Tamoxifen

Intervention Type: DRUG

Dose escalation

Interventions

Tamoxifen

Dose escalation

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ECOG performance status ≤ 1
• Life expectancy ≥ 6 months
• Histologically or cytologically confirmed early, locally advanced or metastatic breast cancer
• Oestrogen receptor positive
• About to start tamoxifen treatment or already on tamoxifen 20mg daily
• Adequate hepatic and renal function

Exclusion Criteria

• Concurrent chemotherapy or radiotherapy
• Treatment with medications that may alter cytochrome P450 (CYP450)3A4/5 and CYP2D6 activities
• History of thrombosis
• History of non-compliance with previous or current treatment;
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent

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

Sponsors

St George Hospital, Australia

OTHER

Sponsor Role: collaborator

Western Sydney Local Health District

OTHER

Sponsor Role: lead

Responsible Party

Howard Gurney

A/Prof Howard Gurney

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Howard Gurney, MBBS,FRACP

Role: PRINCIPAL_INVESTIGATOR

South West Sydney Local Health District

Locations

St George Hospital

Sydney, New South Wales, Australia

Westmead Cancer Care Centre

Westmead, New South Wales, Australia

Countries

Australia

Other Identifiers

TADE study

Identifier Type: -

Identifier Source: org_study_id