Pharmacokinetic Study of Doxorubicin in Children With Cancer
Overview[ - collapse ][ - ]
| Purpose | Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity . |
|---|---|
| Condition | Wilms Tumor Neuroblastoma Soft Tissue Sarcoma Acute Lymphoblastic Leukemia |
| Intervention | Drug: doxorubicin |
| Phase | Phase 2 |
| Sponsor | University Hospital Muenster |
| Responsible Party | University Hospital Muenster |
| ClinicalTrials.gov Identifier | NCT01095926 |
| First Received | March 22, 2010 |
| Last Updated | June 27, 2013 |
| Last verified | March 2010 |
Tracking Information[ + expand ][ + ]
| First Received Date | March 22, 2010 |
|---|---|
| Last Updated Date | June 27, 2013 |
| Start Date | May 2010 |
| Estimated Primary Completion Date | May 2013 |
| Current Primary Outcome Measures | Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia [Time Frame: 24h] [Designated as safety issue: No]Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions. |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Pharmacokinetic Study of Doxorubicin in Children With Cancer |
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| Official Title | Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia |
| 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 |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
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| Intervention | Drug: doxorubicin blood sampling before, during and after doxorubicin administration |
| Study Arm (s) | Experimental: Doxorubicin |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Completed |
|---|---|
| Estimated Enrollment | 101 |
| Estimated Completion Date | May 2013 |
| Estimated Primary Completion Date | February 2013 |
| Eligibility Criteria | Inclusion Criteria: - 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 Exclusion Criteria: - prior cardiac problems |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | France, Germany, Italy, United Kingdom |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01095926 |
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| Other Study ID Numbers | EPOC-MS-001 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University Hospital Muenster |
| Study Sponsor | University Hospital Muenster |
| Collaborators | Not Provided |
| Investigators | Study Chair: Joachim Boos, MD, Prof. University Hospital Muenster |
| Verification Date | March 2010 |
Locations[ + expand ][ + ]
| Centre Oscar Lambret | Lille, France |
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| MD Nicolas Andre, National Study Manager France | Marseille, France |
| CHU La Timone | Marseille, France |
| CHU Nancy | Nancy, France |
| CHU Nantes | Nantes, France |
| Institut curie | Paris, France |
| Institut Gustanve Roussy | Paris, France |
| Universitätsklinikum Essen | Essen, Germany |
| Universitätsklinikum Frankfurt | Frankfurt, Germany, 60690 |
| Universitätsklinikum Freiburg | Freiburg, Germany, 79106 |
| Universitätsklinikum Kiel | Kiel, Germany |
| Universitätsklinikum Münster | Münster, Germany, 48149 |
| Klinikum Stuttgart | Stuttgart, Germany |
| Prof. Maurizio D'Incalci, National Study Manager Italy | Milan, Italy |
| Università degli Studi di Milano | Monza, Italy |
| Clinica di Oncoematologia Pediatrica | Padova, Italy |
| Università Cattolica di Roma | Rome, Italy |
| 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 |