To investigate the relationship fo the pharmacokineticsof the probe drug (dextromethorphan) and tamoxifen.
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic sampling for tamoxifen and dextromethorphan.
The relationship between clearance of tamoxifen and of dextromethorphan.
Secondary outcome
The intra-patient variability in pharmacokinetics of tamoxifen and
dextromethorphan.
The effects of known polymorfismes in CYP2D6 and CYP3A and other relevant
medication metabolizing enzyms and transporters for the pharmacokinetics of
tamoxifen and dextromethorphan.
Background summary
Tamoxifen is frquently used in the treatment of breast cancer patients in
adjuvant and metastasized setting. In comparison with cytostatics the
side-effects of tamoxifen are less in number, but could be dose-limiting and
potentially life-threathening (for example thrombolic complications,
endometrial carcinoma). It is unpredictable at the start of treatment which
patients will receive such side-effects. Hence, it is important to devellop
good predictors.
After intake tamoxifen is metabolised by cytochrome P450 iso-enzymes (for
example CYP2D6, CYP3A4, CYP3A5) in active metabolites, such as endoxifen. The
formation of endoxifen is determinant for the effect and toxicity of tamoxifen.
Recent studies have proven the inter-individual variability in pharmacokinetics
of tamoxifen, leading up to different respons en toxicity profile between
patients. The inter-individual variability can be influenced by many facotrs,
including co-medication, life-style and genetic variation. Recently the
relatiuonship between CYP2D6 polymorfismes and the pharamcokinetics, clinical
outcome and toxicity of tamoxifen has been proven. At this moment the use of
genotyping for CYP2D6 is under investigation. However, the presence of other
iso-enzymes such as CYP3A, responsible for the conversion of 90% of tamoxifen
and life-style are not taken into account in this investigation. To adjust for
these factors, a phenotype probe, which stimulates the metabolism of tamoxifen,
would be hopefullly a beter prognostic marker for the pharmacokinetics of
tamoxifen and possibly even for its therapeutic effect and toxicity.
Study objective
To investigate the relationship fo the pharmacokineticsof the probe drug
(dextromethorphan) and tamoxifen.
Study design
Single center pharmacokinetics study to investigate the relationship between
tamoxifen and dextromethorphan
Study burden and risks
Patients wil be admitted for one day for pharmacokinetic sampling.
Patients will be asked to keep record of a diary for monitoring of compliance
of tamoxifen purpose.
Groene Hilledijk 301
3075 EA Rotterdam
NL
Groene Hilledijk 301
3075 EA Rotterdam
NL
Listed location countries
Age
Inclusion criteria
Histological or cytological confirmed breast cancer
indication for treatment with monotherapy tamoxifen
18 years of age or older
written informed consent
adequate renal, hepatological and hematological lab results
Exclusion criteria
pregnant or lactating women
impossibility for oral intake medication
serious illness or instable medical condition
symptomatic central nervous system metastases
use of strong CYP3A and/or P-glycoprotein inhibiting and inducing medication/supplements
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2008-006017-25-NL |
| CCMO | NL25016.078.09 |
| Other | NLxxxxx.xxx.09 |