-To optimize DM-BT by addition of multiple breath sampling and improve it for use in clinical practice-To create a population based pharmacokinetic model based on DM-BT predicting endoxifen serum levels-To identify ideal single or two time points…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Correlation between CYP2D6 phenotype (by 13C-dextromethorphan breath test) and
endoxifen serum levels.
Secondary outcome
none
Background summary
Results from the first amendemt of rtge CYPTAM documentation study have showm
that 13C-dextrometorphan breath test is a good CYP2D6 phenotyping test in
patients with breast cancer using tamoxifen in the adjuvant setting. CYP2D6 is
an important enzyme involved in the conversion of tamoxifen into the active
metabolite endoxifen. Recent literature suggest a treshold serum endoxifen
level, above which the recurrence of breast cancer decreases. We found a good
correlation between the CYP2D6 genotype and breath test results (i.e. CYP2D6
phenotype). However, we found a large intra- and interindividual variation in
breath tet results in patients with the same CYP2D6 genotype.
We hypothesize that this large variation might be due to large dextromethorphan
pharmacokinetics in individuals and to breath test specifications.
Study objective
-To optimize DM-BT by addition of multiple breath sampling and improve it for
use in clinical practice
-To create a population based pharmacokinetic model based on DM-BT predicting
endoxifen serum levels
-To identify ideal single or two time points for breath collection post
ingestion of 13C-DM by correlating DOB*s at specific timepoints with AUC0-240.
-To compare correlation of single sampling versus 9-point sampling DM-BT with
endoxifen serum levels
-To determine intrapatient variability in DM-BT results
-To determine if the *ceiling effect* in clinical CY2D6 phenotype we have
observed in patients with (het)EM genotype could be reversed by an increased
dose of 50 mg of 13C-dextromethorphan
Study design
Second amendement on de CYPTAM study
In the Leiden University Medical Center, 6 patients recruited from the first
amendment on the CYPTAM documentation study, will undergo a
13C-dextromethorphan breath test on 3 following days.
This study is an intervention study with the CYP2D6 phenotyping probe
13C-dextromethorphan.
Intervention
Patients included in the amendment will be given 50 mg 13-C dextromethorphan,
prior to the breath test. Subjects are asked to breath in a plastic bag for 11
times during each breath test.
One sample of blood (10 cc) will be withdrawmn for determination of tamoxifen
and metabolites.
Study burden and risks
Estimated side effects caused by the use of dextrometorphan will be limited and
if present mild. The overall patient*s burden will be limited as only a vena
puncture and a rapid breath test are required.
Albinusdreef 2
2333 ZA Leiden
NL
Albinusdreef 2
2333 ZA Leiden
NL
Listed location countries
Age
Inclusion criteria
1. Pre- and postmenopausal women who have already been using tamoxifen as part of a standard adjuvant therapy for newly diagnosed breast cancer;2. Willing and able to give written informed consent ;3. Age >= 18 years;4. Women who have already been enrolled in the first amendment on the CYPTAM documentation study ((P.07.234): Addition of CYP2D6 phenotyping by a 13C-dextrometorphan breath test (DM-BT)) and are currently on tamoxifen therapy for at least two months.
Exclusion criteria
Inability or unwillingness to fast overnight prior to the study session.
Inability or willingness to abstain from drinking alcohol for 24 h prior to the DM-BT.
A diagnosis of pulmonary disease such as asthma or other respiratory disease associated with hypercapnia.
Existence of metabolic or gastrointestinal disorders which influence absorption and/or gastric emptying.
A demonstrated adverse reaction to previous dextromethorphan exposure.
Impaired hepatic function as defined by >= Grade 3 AST, alkaline phosphatase or total bilirubin or a history of liver chirrosis
Renal insufficiency
Use of medication known to slow gastric emptying or gastrointestinal motility within 24 hours of the breath test (known to slow gastric emptying or gastrointestinal motility •
The use of MAO inhibitors in the last two weeks
Use of dextrometorphan cough syrup/tablets within 24 hours of the breath test.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | EUCTR2007-006270-28-NL |
| CCMO | NL20595.058.07 |