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Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia

Phase 2
17 Years
Not Enrolling
Wilms Tumor, Neuroblastoma, Soft Tissue Sarcoma, Acute Lymphoblastic Leukemia

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Trial Information

Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia

- 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

- 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

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

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia

Outcome Description:

Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.

Outcome Time Frame:


Safety Issue:


Principal Investigator

Joachim Boos, MD, Prof.

Investigator Role:

Study Chair

Investigator Affiliation:

University Hospital Muenster


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

May 2010

Completion Date:

May 2013

Related Keywords:

  • Wilms Tumor
  • Neuroblastoma
  • Soft Tissue Sarcoma
  • Acute Lymphoblastic Leukemia
  • pharmacokinetic
  • doxorubicin
  • cancer
  • troponin
  • natriuretic peptide
  • cardiotoxicity
  • anthracyclines
  • Ewing
  • ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Wilms Tumor
  • Neuroblastoma
  • Sarcoma