Pharmacokinetic Study of Doxorubicin in Children With Cancer (Doxo)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01095926|
Recruitment Status : Completed
First Posted : March 30, 2010
Last Update Posted : June 28, 2013
|Condition or disease||Intervention/treatment||Phase|
|Wilms Tumor Neuroblastoma Soft Tissue Sarcoma Acute Lymphoblastic Leukemia||Drug: doxorubicin||Phase 2|
- 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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||101 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||February 2013|
|Actual Study Completion Date :||May 2013|
blood sampling before, during and after doxorubicin administration
- Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia [ Time Frame: 24h ]Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
- Assess interindividual, intraindividual and residual variability of PK parameters in children [ Time Frame: 24h ]Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
- Assess relationship between PK parameters and patient characteristics [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01095926
|Centre Oscar Lambret|
|CHU La Timone|
|MD Nicolas Andre, National Study Manager France|
|Institut Gustanve Roussy|
|Frankfurt, Germany, 60690|
|Freiburg, Germany, 79106|
|Münster, Germany, 48149|
|Prof. Maurizio D'Incalci, National Study Manager Italy|
|Università degli Studi di Milano|
|Clinica di Oncoematologia Pediatrica|
|Università Cattolica di Roma|
|Birmingham Childrens Hospital|
|Birmingham, United Kingdom|
|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|
|Study Chair:||Joachim Boos, MD, Prof.||University Hospital Muenster|