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

Sponsor

Western Sydney Local Health District (Other)

Overall Status

Completed

CT.gov ID

NCT01075802

Collaborator

St George Hospital, Australia (Other)

121

Enrollment

Locations

Arm

33.1

Duration (Months)

60.5

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer CYP2D6 Polymorphism	Drug: Tamoxifen	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

A Multi-Centre Study of Tamoxifen Dose Escalation Study in Breast Cancer Patients With CYP2D6 Polymorphisms

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tamoxifen Dose escalation of tamoxifen in patients with low endoxifen levels	Drug: Tamoxifen Dose escalation

Arm

Intervention/Treatment

Experimental: Tamoxifen

Dose escalation of tamoxifen in patients with low endoxifen levels

Drug: Tamoxifen

Dose escalation

Outcome Measures

Primary Outcome Measures

Effects of genotype of CYP2D on plasma and serum concentration of tamoxifen and its metabolites, with consequent recommendation for dosage adjustment [dose escalation over 40 weeks]
To test whether Tamoxifen dose escalation in patients with genetic polymorphism of CYP2D6 will increase endoxifen blood levels to a target level [Dose escalation over 40 weeks]
Correlate tamoxifen and its metabolites concentration with tamoxifen side effects [dose escalation over 40 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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