Pharmacokinetic Study of Doxorubicin in Children With Cancer (Doxo)

June 27, 2013 updated by: University Hospital Muenster

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lille, France
        • Centre Oscar Lambret
      • Marseille, France
        • CHU La Timone
      • Marseille, France
        • MD Nicolas Andre, National Study Manager France
      • Nancy, France
        • CHU Nancy
      • Nantes, France
        • CHU Nantes
      • Paris, France
        • Institut Curie
      • Paris, France
        • Institut Gustanve Roussy
  • Germany
      • Essen, Germany
        • Universitätsklinikum Essen
      • Frankfurt, Germany, 60690
        • Universitätsklinikum Frankfurt
      • Freiburg, Germany, 79106
        • Universitätsklinikum Freiburg
      • Kiel, Germany
        • Universitätsklinikum Kiel
      • Münster, Germany, 48149
        • Universitätsklinikum Münster
      • Stuttgart, Germany
        • Klinikum Stuttgart
  • Italy
      • Milan, Italy
        • Prof. Maurizio D'Incalci, National Study Manager Italy
      • Monza, Italy
        • Universita degli Studi di Milano
      • Padova, Italy
        • Clinica di Oncoematologia Pediatrica
      • Rome, Italy
        • Università Cattolica di Roma
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Childrens Hospital
      • Leeds, United Kingdom
        • St James's University Hospital
      • London, United Kingdom
        • Great Ormond Street Hospital for Children
      • Manchester, United Kingdom
        • Royal Manchester Childrens Hospital
      • Newcastle upon Tyne, United Kingdom
        • Prof. Alan Boddy, National Study Manager UK
      • Newcastle upon Tyne, United Kingdom
        • Royal Victoria Infirmary, Sir James Spence Institute of Child Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24h

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24h
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.
24h
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.
5 years
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.
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Muenster

Investigators

  • Study Chair: Joachim Boos, MD, Prof., University hospital Muenster

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

March 22, 2010

First Submitted That Met QC Criteria

March 29, 2010

First Posted (Estimate)

March 30, 2010

Study Record Updates

Last Update Posted (Estimate)

June 28, 2013

Last Update Submitted That Met QC Criteria

June 27, 2013

Last Verified

March 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPOC-MS-001
  • 2009-011454-17 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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