Pharmacokinetic Study of Doxorubicin in Children With Cancer
- Conditions
- Wilms TumorNeuroblastomaSoft Tissue SarcomaAcute Lymphoblastic Leukemia
- Interventions
- Registration Number
- NCT01095926
- Lead Sponsor
- University Hospital Muenster
- Brief 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 101
- patients ≤ 17 years of age
- plan to receive at least two cycles of doxorubicin
- must be enrolled in a national or European protocol for treatment of Wilms Tumours, Neuroblastoma, Soft tissue sarcoma, Ewing Sarcoma or Acute lymphoblastic leukaemia and must be treated with doxorubicin according to that protocol Or Patients < 3 years enrolled or listed in any national or European study protocol for any paediatric malignancy. Treatment with doxorubicin has to be according to that protocol.
- Parents or legal representative(s) must provide written informed consent to participate in the trial according to national regulations. Patients that are able to understand should provide assent to participate in the trial.
- Life expectancy of at least 3 month
- Karnofsky performance status of ≥ 70%
- Additional blood withdrawal is acceptable for the patient. The decision is left to the investigator
- prior cardiac problems
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Doxorubicin doxorubicin -
- Primary Outcome Measures
Name Time Method Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia 24h Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
- Secondary Outcome Measures
Name Time Method Assess interindividual, intraindividual and residual variability of PK parameters in children 24h Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
Assess relationship between PK parameters and patient characteristics 24h Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
Explore in a preliminary fashion genetic polymorphisms that may influence doxorubicin clearance 5 years Obtain one whole blood sample per patient, if separate consent was given.
Evaluate the potential role of natriuretic peptides and troponin as indicators for subclinical cardiotoxicity 1 month Measure troponin T, troponin I, BNP, NT-proBNP, NT-proANP. Collect samples at two different doxorubicin infusions before and up to 1month after doxorubicin administration.
Trial Locations
- Locations (23)
CHU Nantes
🇫🇷Nantes, France
Università Cattolica di Roma
🇮🇹Rome, Italy
Centre Oscar Lambret
🇫🇷Lille, France
Universitätsklinikum Kiel
🇩🇪Kiel, Germany
CHU La Timone
🇫🇷Marseille, France
CHU Nancy
🇫🇷Nancy, France
MD Nicolas Andre, National Study Manager France
🇫🇷Marseille, France
Institut curie
🇫🇷Paris, France
Institut Gustanve Roussy
🇫🇷Paris, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Prof. Maurizio D'Incalci, National Study Manager Italy
🇮🇹Milan, Italy
Università degli Studi di Milano
🇮🇹Monza, Italy
Klinikum Stuttgart
🇩🇪Stuttgart, Germany
Birmingham Childrens Hospital
🇬🇧Birmingham, United Kingdom
Clinica di Oncoematologia Pediatrica
🇮🇹Padova, Italy
St James's University Hospital
🇬🇧Leeds, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom
Royal Manchester Childrens Hospital
🇬🇧Manchester, United Kingdom
Prof. Alan Boddy, National Study Manager UK
🇬🇧Newcastle upon Tyne, United Kingdom
Royal Victoria Infirmary, Sir James Spence Institute of Child Health
🇬🇧Newcastle upon Tyne, United Kingdom