NCT01095926

Pharmacokinetic Study of Doxorubicin in Children With Cancer

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 101 (actual)
• Sponsor: University Hospital Muenster · Academic / Other
• Sex: All
• Age: 17 Years
• Healthy volunteers: Not accepted

Summary

Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .

Detailed description

* 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

Conditions

• Wilms Tumor
• Neuroblastoma
• Soft Tissue Sarcoma
• Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	doxorubicin	blood sampling before, during and after doxorubicin administration

Timeline

• Start date: 2010-05-01
• Primary completion: 2013-02-01
• Completion: 2013-05-01
• First posted: 2010-03-30
• Last updated: 2013-06-28

Locations

23 sites across 4 countries: France, Germany, Italy, United Kingdom