Clinical trial NCT01075802: Study of Tamoxifen Dose Escalation in Breast Cancer Patients With CYP2D6 Polymorphisms
Official title: A Multi-Centre Study of Tamoxifen Dose Escalation Study in Breast Cancer Patients With CYP2D6 Polymorphisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
CYP2D6 Polymorphism
Keywords: Breast cancer
Tamoxifen
Endoxifen
polymorphism of CYP2D6
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
Collaborators: name: St George Hospital, Australia
First posted: 2010-02-25
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: Effects of genotype of CYP2D on plasma and serum concentration of tamoxifen and its metabolites, with consequent recommendation for dosage adjustment
timeFrame: dose escalation over 40 weeks
measure: To test whether Tamoxifen dose escalation in patients with genetic polymorphism of CYP2D6 will increase endoxifen blood levels to a target level
timeFrame: Dose escalation over 40 weeks
measure: Correlate tamoxifen and its metabolites concentration with tamoxifen side effects
timeFrame: dose escalation over 40 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: St George Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Cancer Care Centre
state: New South Wales
Study officials:
affiliation: South West Sydney Local Health District
name: Howard Gurney, MBBS,FRACP
role: PRINCIPAL_INVESTIGATOR
References: