Trial Information

Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia

- Paediatric patients up to the age of 17 years will be included. Number and time points
of PK sampling will depend on age and tumour type.

- PK samples will be collected from two doxorubicin administrations. Analyzing samples
from two doxorubicin administrations will allow distinguishing between interindividual,
intraindividual and residual variability.

- Doxorubicin and its major metabolite doxorubicinol will be measured in plasma using
HPLC

- In addition, the natriuretic peptide BNP and the precursors NT-pro ANP and NT-proBNP as
well as troponin T will be measured in plasma up to 28 days after doxorubicin
administration to evaluate their use as clinical markers for cardiotoxicity.

- A data set of max 5 samples (3 +2 (in the 1st + 2nd Doxorubicin sampling periods)) will
be collected in the younger children (< 3 years) and a data set of max. 8 samples ( 5 +
3) will be collected in the older children. Samples will be taken at predefined time
points/ time intervals.

- An additional DNA sample will be taken and analyzed for genetic polymorphisms. The
influence of genotype on pharmacokinetics and metabolism will be investigated by
appropriate statistical methods, including population pharmacokinetic analyses. Genes
to study would include MDR1 and SLC22A16, both involved in the transport of doxorubicin
and AKR1A1 and CBR1, both involved in the reduction of doxorubicin to doxorubicinol.
Selected genotypes will be incorporated as covariates into the population
pharmacokinetic models developed. The potential impact of genetic variation will be
evaluated in the context of other sources of variability such as age, weight, gender
etc