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

Breast Cancer Clinical Trial

— TADE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01075802
• Other study ID #: TADE study
• Status: Completed
• Phase: N/A
• First received: February 24, 2010
• Last updated: May 3, 2013
• Start date: March 2010
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: Western Sydney Local Health District
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: December 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• CYP2D6 Polymorphism

Intervention

Drug:
• Tamoxifen
Dose escalation

Locations

Country	Name	City	State
Australia	St George Hospital	Sydney	New South Wales
Australia	Westmead Cancer Care Centre	Westmead	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Western Sydney Local Health District	St George Hospital, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	Correlate tamoxifen and its metabolites concentration with tamoxifen side effects		dose escalation over 40 weeks	Yes