Primary objective:The primary objective of this study is to define the differences in the interaction between oral dexamethasone and aprepitant and the interaction between iv dexamethasone and aprepitant.Secondary objective:The secondary objective…
ID
Source
Brief title
Condition
- Gastrointestinal signs and symptoms
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic parameters (i.e. clearance and volume of distribution) will be
assessed using non-linear mixed effects modelling (NONMEM). Influence of
relevant co-variates will be assessed by standard model building methods.
Secondary outcome
NA
Background summary
Prophylaxis on chemotherapy induced nausea and vomiting (CINV) is still a major
problem in patients receiving highly emetogenic therapy, which has important
consequences for quality of life during chemotherapy administration. Despite
standardized prophylaxis patients receiving highly emetogenic therapy achieve a
variable complete response rate (no vomiting and no rescue treatment) of
70-90%.6-8 One of the possible explanations could be that the interaction
between oral dexamethasone and aprepitant is different from the interaction
between iv dexamethasone and aprepitant. Aprepitant and dexamethasone show a
mutual drug-drug interaction, which has been studied in adults. As a rule of
thumb a 50% dose-reduction of dexamethasone is applied with treatment is
combined with aprepitant. However, the difference in interaction between these
dosage forms has not been studied yet. From pharmacological perspective, it can
be expected that the interaction is stronger for orally given dexamethasone,
since aprepitant can inhibit CYP3A4-enzymes in the GI-tract as well, which can
alter the absorption of dexamethasone. With the results of this proposed study
the differences in the interaction between oral dexamethasone and aprepitant
and the interaction between iv dexamethasone and aprepitant will be studied.
Study objective
Primary objective:
The primary objective of this study is to define the differences in the
interaction between oral dexamethasone and aprepitant and the interaction
between iv dexamethasone and aprepitant.
Secondary objective:
The secondary objective of this study is to describe the PK of aprepitant and
dexamethasone together with the results of an ongoing study in pediatric
patients (in the Princess Maxima Center for pediatric oncology), to describe
the age dependent differences in PK of dexamethasone and aprepitant.
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 of aprepitant and dexamethasone,
and their interaction in patients with cancer. Insight in the PK of these
antiemetic drugs may result in improved dosing guidelines and/or individualized
dosing regimens based on therapeutic drug monitoring, ultimately resulting
better anti-emetic control. The only consequence of study participation is that
additional blood samples will be withdrawn. The here applied sampling strategy
is minimally invasive. The volume of blood that is withdrawn for the study does
not exceed the recommended maximum; see 6.3.3 Blood sampling for
pharmacokinetics. Sampling, using a flexible time scheme, will only be
requested during regular hospital visits.
Plesmanlaan 121
Amsterdam 1066CX
NL
Plesmanlaan 121
Amsterdam 1066CX
NL
Listed location countries
Age
Inclusion criteria
1. Planned to receive chemotherapy intravenously as regular treatment (standard
of care);
2. Receiving dexamethasone with or without aprepitant as standard of care
3. Receiving the chemotherapy and anti-emetics during hospitalized treatment.
4. Age >=18;
5. Signed Informed consent form (ICF) prior to participation in the study;
6. Able and willing to undergo blood draw for the study (two different days, 6
times per day) and does not have any condition that makes participation
disadvantageous.
7. For women: not pregnant
8. No use of strong CYP3A4 substrates or inhibitors within 7 days or CYP3A4
inducers within 30 days of treatment (appendix 2);
Exclusion criteria
See 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 | NL75380.031.20 |