we propose a pilot PK study to assess: 1) The interaction between aprepitant and dexamethasone in children using both antiemetogenic agents at the same time, to optimize the dose of both agents in children of different age groups.2) The feasibility…
ID
Source
Brief title
Condition
- Gastrointestinal disorders
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Population PK model dexamethason/ aprepitant.
Secondary outcome
Feasibility PeNAT score on nausea intensity in clinical practice
Background summary
Children treated with moderate to high emetogenic chemotherapy appear to have
worse anti-emetic control when compared to adults (i.e. approximately 50%
compared to 70-80% in adults), which has important consequences for quality of
life during chemotherapy administration. One potential explanation for the
inferior efficacy of regular anti-emetic therapy in children is that suboptimal
doses and duration of combined aprepitant and dexamethasone in children are
used, which - together with a 5-HT3 antagonist - is the gold standard of
current anti-emetic therapy. Aprepitant and dexamethasone show a mutual
drug-drug interaction, which has been studied in adults, but this has not been
studied in children. As a rule of thumb in children 50% dose-reduction of
dexamethasone is applied with treatment is combined with aprepitant, which was
extrapolated from findings in adults. This may result in sub-optimal dosing in
children and may at least partly explain the differences in anti-emetic control
between adults and children. Therefore, this pharmacokinetic interaction (PK)
also needs to be characterized in children. Moreover, children of different age
groups use different formulations which may also impact on drug exposure.
Another important aspect is that aprepitant exposure is known to be influenced
by chemotherapy, as summarized by Patel et al. 2017. There is almost no data of
aprepitant in chemotherapy regimens frequently used in children.
Study objective
we propose a pilot PK study to assess:
1) The interaction between aprepitant and dexamethasone in children using both
antiemetogenic agents at the same time, to optimize the dose of both agents in
children of different age groups.
2) The feasibility of using the validated PeNAT score on nausea intensity in
clinical practice.
Study design
prospective observational study
Study burden and risks
The patient has no direct benefit from participating in this study. The data
obtained in this study will be used to assess the population PK to develop an
optimized dosing regimen of aprepitant and dexamethasone in children.
Participation in this pilot study is minimally invasive and will include
additional blood samples (maximum of 6 samples of 1 ml) and questionnaires on
nausea and vomiting. The blood samples will be taken from the central line,
which is inserted as standard of care in the context of chemotherapeutic
treatment. The volume of blood that is withdrawn for the study does not exceed
the recommended maximum. Sampling, using a flexible time scheme, will only be
requested during regular hospital visits.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
1. Planned to receive chemotherapy intravenously as regular treatment (standard of care);
2. Receiving granisetron/ondansetron; dexamethasone and/or aprepitant as standard of care
3. Age * 6maanden en *19 years;
4. Informed consent form (ICF) signed prior to participation in the study;
5. A present central line to sample blood for pharmacokinetics;
6. No Down syndrome or other syndromes that may influence regular dosing or no other disease/circumstances that may influence the participation of the subject in a negative way;
7. No use of strong CYP3A4 substrates or inhibitors within 7 days or CYP3A4 inducers within 30 days of treatment (appendix 2);
8. No current pregnancy
9. During fertile age, extra none-hormonal contraceptives during the days of emend until 2 months after
Exclusion criteria
see above, all described in the inclusion criteria
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL67072.078.18 |
| OMON | NL-OMON24991 |