No registrations found.
ID
Source
Brief title
Health condition
Cancer
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to assess the pharmacokinetics of various cytotoxic agents (carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate and vincristine) and their known metabolites (if applicable) in children to characterize the age-related changes in pharmacokinetics.
Secondary outcome
- To determine the influence of overweight and obesitas (for cut off points for BMI, see table 4 in Cole et al, 200053) on the pharmacokinetics of carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate and vincristine and their known metabolites (if applicable) in pediatric patients (0-17 years).
- To correlate pharmacokinetics of pediatric patients with clinical and laboratory toxicity.
Background summary
Rationale: Little is known about the PK of the various classes of chemotherapy in children. Insight in the PK of the various classes of chemotherapy in children and, especially, in infants may result in improved dosing guidelines and/or individualized dosing regimens based on therapeutic drug monitoring, ultimately resulting in better clinical outcome. The aim is that future dosing of children with cancer will be evidence-based, as a result of the population PK data that will be generated with this project. As the projects covers several different chemotherapeutic drugs, the results will be highly relevant, as it will optimize the regimen in total, instead of only studying one single drug.
Objective: To assess the pharmacokinetics of various cytotoxic agents (carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate and vincristine) and their known metabolites (if applicable) in children to characterize the age-related changes in pharmacokinetics.
Study design: Prospective observational study
Study population: Patients aged 0-17 years treated in the PMC who will receive intravenously administered carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate or vincristine, that all have a present central line to sample blood for pharmacokinetics.
Main study parameters/endpoints: 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.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: 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 various classes of chemotherapeutic agents in children and infants with cancer. The only consequence of study participation is that additional blood samples (maximum of 8 samples of 1 ml once or twice) will be withdrawn. The here applied sampling strategy is minimally invasive, since all the patients that are included already have a central line. 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.
Study objective
Thus, insight in the PK of the various classes of chemotherapy in children and, especially, in infants may result in improved dosing guidelines and/or individualized dosing regimens based on therapeutic drug monitoring, ultimately resulting in better clinical outcome. The aim is that future dosing of children with cancer will be evidence-based, as a result of the population PK data that will be generated with this project. As the projects covers several different chemotherapeutic drugs, the results will be highly relevant, as it will optimize the regimen in total, instead of only studying one single drug.
Study design
START of the study: 01-02-2019
END of the study: 01-02-2022
Inclusion criteria
1. Planned to receive carboplatin, cisplatin, cytarabine, dactinomycin, daunorubicin, doxorubicin, etoposide, methotrexate or vincristine intravenously as regular treatment (standard of care);
2. Age ≤18 years;
3. Informed consent form (ICF) signed prior to participation in the study;
4. A present central line to sample blood for pharmacokinetics
Exclusion criteria
1. Down syndrome;
2. For fertile adolescent girls: pregnancy (orally inquired, a test is not necessary);
3. Any other disease/circumstances that may influence the participation of the subject in a negative way
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7527 |
| CCMO | NL63037.078.18 |
| OMON | NL-OMON55747 |