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Pharmacokinetic Study of Doxorubicin in Children With Cancer (Doxo)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01095926
Recruitment Status : Completed
First Posted : March 30, 2010
Last Update Posted : June 28, 2013
Sponsor:
Information provided by (Responsible Party):
University Hospital Muenster

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

Condition or disease Intervention/treatment Phase
Wilms Tumor Neuroblastoma Soft Tissue Sarcoma Acute Lymphoblastic Leukemia Drug: doxorubicin Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 101 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2010
Actual Primary Completion Date : February 2013
Actual Study Completion Date : May 2013


Arm Intervention/treatment
Experimental: Doxorubicin Drug: doxorubicin
blood sampling before, during and after doxorubicin administration




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01095926


Locations
Show Show 23 study locations
Sponsors and Collaborators
University Hospital Muenster
Investigators
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Study Chair: Joachim Boos, MD, Prof. University Hospital Muenster
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Responsible Party: University Hospital Muenster
ClinicalTrials.gov Identifier: NCT01095926    
Other Study ID Numbers: EPOC-MS-001
2009-011454-17 ( EudraCT Number )
First Posted: March 30, 2010    Key Record Dates
Last Update Posted: June 28, 2013
Last Verified: March 2010
Keywords provided by University Hospital Muenster:
pharmacokinetic
doxorubicin
cancer
troponin
natriuretic peptide
cardiotoxicity
anthracyclines
Ewing
ALL
Additional relevant MeSH terms:
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Leukemia
Sarcoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neuroblastoma
Wilms Tumor
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective and Soft Tissue
Leukemia, Lymphoid
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, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn
Doxorubicin