Pharmacokinetic Study of Doxorubicin in Children With Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital Muenster
ClinicalTrials.gov Identifier:
NCT01095926
First received: March 22, 2010
Last updated: June 27, 2013
Last verified: March 2010
  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:


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.


Enrollment: 101
Study Start Date: May 2010
Study Completion Date: May 2013
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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: June 27, 2013
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:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neuroblastoma
Sarcoma
Leukemia
Wilms Tumor
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
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
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn
Doxorubicin

ClinicalTrials.gov processed this record on October 16, 2014