No registrations found.
ID
Source
Brief title
Health condition
relationship between the CYP3A and CYP2D6 probe dextromethorphan and the pharmacokinetics of tamoxifen in breast cancer patients who require tamoxifen monotherapy
Sponsors and support
Department of Internal Oncology
Daniel den Hoed Center
Erasmus University
Groene Hilledijk 301
3075 AE Rotterdam
The Netherlands
tel 0031107041331
fax 0031107041003
j.verweij@erasmusmc.nl
Daniel den Hoed Center
Erasmus University
Groene Hilledijk 301
3075 AE Rotterdam
The Netherlands
tel 0031107041331
fax 0031107041003
j.verweij@erasmusmc.nl
Intervention
Outcome measures
Primary outcome
Relationships between dextromethorphan clearance and the clearance of tamoxifen in breast cancer patients.
Secondary outcome
Relationships between other PK-parameters (AUC, Cmax and Tmax); effects of known polymorphisms in CYP2D6 and CYP3A and other relevant drug metabolizing enzymes and transporters on the pahrmacokinetics of tamoxifen and dextromethorphan.
Background summary
In this observational trial we would like to study the possible correlation between the probe-drug dextromethrophan and tamoxifen pharmacokinetics. In case a good correlation is available, this might help in a stepwise development of truly individualizing tamoxifen treatment. Study objectives are relationships between dextromethorphan clearance and the clearance of tamoxifen in breast cancer patients; relationships between other PK-parameters (AUC, Cmax and Tmax); effects of known polymorphisms in CYP2D6 and CYP3A and other relevant drug metabolizing enzymes and transporters on the pahrmacokinetics of tamoxifen and dextromethorphan. In one center (Erasmus Medical Center at Rotterdam, the netherlands), a total of 37 eligable patients, treated with a dose of 20 or 40 mg of tamoxifen, depending on their indication, will be given 30 mg dextromethorphan orally at day 1. Pharmacokinetic sampling will be performed at given time-points (pre, 30 min-24hours, in total 9 sampling time points). For dextromethorphan, blood samples will be processed to plasma and stored until analysis by a validated liquid chromatography tandem mass spectometry method. For tamoxifen, blood samples will be processed to serum and stored until analysis by a validated liquid chromatography tandem mass spectometry method.
Study objective
In this observational trial we would like to study the possible correlation between the probe-drug dextromethrophan and tamoxifen pharmacokinetics. In case a good correlation is available, this might help in a stepwise development of truly individualizing tamoxifen treatment.
Study design
1. Day -28/-1: informed consent;
2. Day 1: pharmaokinetic sampling (pre, 30 min-24hours in total 9 sampling time points).
Intervention
Observational study with pharmacokinetic sampling.
Department of Internal Oncology
Daniel den Hoed Center
Erasmus University
Groene Hilledijk 301
Rotterdam 3075 AE
The Netherlands
+31 (0)107041906
f.devos@erasmusmc.nl
Department of Internal Oncology
Daniel den Hoed Center
Erasmus University
Groene Hilledijk 301
Rotterdam 3075 AE
The Netherlands
+31 (0)107041906
f.devos@erasmusmc.nl
Inclusion criteria
1. Histological or cytological confirmed history of breast cancer for which treatment with tamoxifen monotherapy is indicated;
2. Age> or = 18 years;
3. WHO 0 or 1;
4. Adequate renal and hepatic functions;
5. Adequate hematological function;
6. Written informed consent;
7. Use of tamoxifen monotherapy for at least 3 weeks.
Exclusion criteria
1. Pregnant or lactating patients;
2. Patients with reproductive potential must use a reliable method of contraception;
3. Impossibility to take oral drugs;
4. Serious illness or medical unstable condition requiring treatment;
5. Symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of ijnformed consent;
6. Unwillingness to abstain form grapefruit (juice), (herbal) dietary supplements, herbals and over the counter medication (except paracetamol and ibuprofen) and other drugs known for to seriously interact with CYP3A and/or ABCB1 and/or ABCG2 during the study period;
7. Use of strong CYP3A and/or P-glycoprotein inhibiting and inducing medication, dietary supplements or other inhibiting compounds.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL1653 |
| NTR-old | NTR1751 |
| Other | MEC : 09-YYY |
| ISRCTN | ISRCTN wordt niet meer aangevraagd |