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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; CYP2D6 Polymorphism
• Intervention / Treatment: Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • St George Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Cancer Care Centre

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• 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: Tamoxifen; Dose escalation of tamoxifen in patients with low endoxifen levels	Drug: Tamoxifen; Dose escalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District
• Collaborators: St George Hospital, Australia
• Investigators: Principal Investigator: Howard Gurney, MBBS,FRACP, South West Sydney Local Health District

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 25, 2010

Study Record Updates

• Last Update Posted (Estimate): May 6, 2013
• Last Update Submitted That Met QC Criteria: May 3, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Tamoxifen; Breast cancer; Endoxifen; polymorphism of 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: TADE study