Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003787

Trial Description

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Title

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

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Trial Acronym

Doxo

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URL of the Trial

[---]*

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Brief Summary in Lay Language

Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the
predictive role of troponin and natriuretic peptides for anthracycline-induced
cardiotoxicity .

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Brief Summary in Scientific Language

- 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

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Organizational Data

  •   DRKS00003787
  •   2012/05/04
  •   2010/03/22
  •   yes
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Secondary IDs

  •   2009-011454-17 
  •   NCT01095926  (ClinicalTrials.gov)
  •   EPOC-MS-001  (University Hospital Muenster)
  •   2009-011454-17 
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Health Condition or Problem studied

  •   Wilms Tumor
  •   Neuroblastoma
  •   Soft Tissue Sarcoma
  •   Acute Lymphoblastic Leukemia
  •   C91.0 -  Acute lymphoblastic leukaemia
  •   C64 -  Malignant neoplasm of kidney, except renal pelvis
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Interventions/Observational Groups

  •   Drug: doxorubicin
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
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Primary Outcome

- 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.

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Secondary Outcome

- 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.

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Countries of Recruitment

  •   France
  •   Germany
  •   Italy
  •   United Kingdom
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Locations of Recruitment

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Recruitment

  •   [---]*
  •   2010/05/31
  •   100
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   17   Years
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Additional 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

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Exclusion Criteria

- prior cardiac problems

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Addresses

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    • University Hospital Muenster
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    • University Hospital Muenster
    • Joachim Boos, MD, Prof. 
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    • University Hospital Muenster
    • Joachim Boos, MD, Prof. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting complete, follow-up complete
  •   2013/05/01
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   53
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.