Pharmacokinetic Study of Doxorubicin in Children With Cancer
The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by University Hospital Muenster.
Recruitment status was Active, not recruiting
Recruitment status was Active, not recruiting
Sponsor:
University Hospital Muenster
Information provided by (Responsible Party):
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT01095926
First received: March 22, 2010
Last updated: December 6, 2012
Last verified: March 2010
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .
| Condition | Intervention | Phase |
|---|---|---|
|
Wilms Tumor Neuroblastoma Soft Tissue Sarcoma Acute Lymphoblastic Leukemia |
Drug: doxorubicin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia |
Resource links provided by NLM:
Genetics Home Reference related topics:
neuroblastoma
MedlinePlus related topics:
Cancer
Chronic Lymphocytic Leukemia
Leukemia
Neuroblastoma
Soft Tissue Sarcoma
Wilms' Tumor
U.S. FDA Resources
Further study details as provided by University Hospital Muenster:
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.
Secondary Outcome Measures:
- Assess interindividual, intraindividual and residual variability of PK parameters in children [ Time Frame: 24h ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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.
| Estimated Enrollment: | 100 |
| Study Start Date: | May 2010 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | February 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Doxorubicin |
Drug: doxorubicin
blood sampling before, during and after doxorubicin administration
|
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
Eligibility| Ages Eligible for Study: | up to 17 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01095926
Locations
| France | |
| Centre Oscar Lambret | |
| Lille, France | |
| 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 | |
| Germany | |
| 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 | |
| Italy | |
| 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 | |
| United Kingdom | |
| 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 | |
Sponsors and Collaborators
University Hospital Muenster
Investigators
| Study Chair: | Joachim Boos, MD, Prof. | University Hospital Muenster |
More Information
Additional Information:
No publications provided
| Responsible Party: | University Hospital Muenster |
| ClinicalTrials.gov Identifier: | NCT01095926 History of Changes |
| Other Study ID Numbers: | EPOC-MS-001, 2009-011454-17 |
| Study First Received: | March 22, 2010 |
| Last Updated: | December 6, 2012 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices United Kingdom: Medicines and Healthcare Products Regulatory Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Italy: Ethics Committee |
Keywords provided by University Hospital Muenster:
|
pharmacokinetic doxorubicin cancer troponin natriuretic peptide |
cardiotoxicity anthracyclines Ewing ALL |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Wilms Tumor Neuroblastoma Sarcoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms, Complex and Mixed Kidney Neoplasms Urologic Neoplasms |
Urogenital Neoplasms Neoplasms by Site Neoplastic Syndromes, Hereditary Kidney Diseases Urologic Diseases Genetic Diseases, Inborn Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Connective and Soft Tissue Doxorubicin |
ClinicalTrials.gov processed this record on June 18, 2013