NCT01075802

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
121

participants targeted

Target at P50-P75 for not_applicable breast-cancer

Timeline
Completed

Started Mar 2010

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 24, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 25, 2010

Completed
4 days until next milestone

Study Start

First participant enrolled

March 1, 2010

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

May 6, 2013

Status Verified

May 1, 2013

Enrollment Period

2.6 years

First QC Date

February 24, 2010

Last Update Submit

May 3, 2013

Conditions

Breast CancerCYP2D6 Polymorphism

Keywords

Breast cancerTamoxifenEndoxifenpolymorphism of CYP2D6

Outcome Measures

Primary Outcomes (3)

  • 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

Study Arms (1)

Tamoxifen

EXPERIMENTAL

Dose escalation of tamoxifen in patients with low endoxifen levels

Drug: Tamoxifen

Interventions

TamoxifenDRUG

Dose escalation

Tamoxifen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

St George Hospital

Sydney, New South Wales, Australia

Location

Westmead Cancer Care Centre

Westmead, New South Wales, 2145, Australia

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

StilbenesBenzylidene CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Howard Gurney, MBBS,FRACP

    South West Sydney Local Health District

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
A/Prof Howard Gurney

Study Record Dates

First Submitted

February 24, 2010

First Posted

February 25, 2010

Study Start

March 1, 2010

Primary Completion

October 1, 2012

Study Completion

December 1, 2012

Last Updated

May 6, 2013

Record last verified: 2013-05

Locations

AU(2)