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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01075802




Registration number
NCT01075802
Ethics application status
Date submitted
24/02/2010
Date registered
25/02/2010
Date last updated
6/05/2013

Titles & IDs
Public title
Study of Tamoxifen Dose Escalation in Breast Cancer Patients With CYP2D6 Polymorphisms
Scientific title
A Multi-Centre Study of Tamoxifen Dose Escalation Study in Breast Cancer Patients With CYP2D6 Polymorphisms
Secondary ID [1] 0 0
TADE study
Universal Trial Number (UTN)
Trial acronym
TADE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
CYP2D6 Polymorphism 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tamoxifen

Experimental: Tamoxifen - Dose escalation of tamoxifen in patients with low endoxifen levels


Treatment: Drugs: Tamoxifen
Dose escalation
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Effects of genotype of CYP2D on plasma and serum concentration of tamoxifen and its metabolites, with consequent recommendation for dosage adjustment
Timepoint [1] 0 0
dose escalation over 40 weeks
Primary outcome [2] 0 0
To test whether Tamoxifen dose escalation in patients with genetic polymorphism of CYP2D6 will increase endoxifen blood levels to a target level
Timepoint [2] 0 0
Dose escalation over 40 weeks
Primary outcome [3] 0 0
Correlate tamoxifen and its metabolites concentration with tamoxifen side effects
Timepoint [3] 0 0
dose escalation over 40 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Diagnosis
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2012
Sample size
Target
Accrual to date
Final
121
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St George Hospital - Sydney
Recruitment hospital [2] 0 0
Westmead Cancer Care Centre - Westmead
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
2145 - Westmead

Funding & Sponsors
Primary sponsor type
Other
Name
Western Sydney Local Health District
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
St George Hospital, Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT01075802
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Howard Gurney, MBBS,FRACP
Address 0 0
South West Sydney Local Health District
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01075802