Pharmacokinetic Study of Doxorubicin in Children With Cancer

NCT ID: NCT01095926

Last Updated: 2013-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

101 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2013-05-31

Brief Summary

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

Detailed Description

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* 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

Conditions

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Wilms Tumor Neuroblastoma Soft Tissue Sarcoma Acute Lymphoblastic Leukemia

Keywords

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pharmacokinetic doxorubicin cancer troponin natriuretic peptide cardiotoxicity anthracyclines Ewing ALL

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Doxorubicin

Group Type EXPERIMENTAL

doxorubicin

Intervention Type DRUG

blood sampling before, during and after doxorubicin administration

Interventions

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doxorubicin

blood sampling before, during and after doxorubicin administration

Intervention Type DRUG

Eligibility Criteria

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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
Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Muenster

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joachim Boos, MD, Prof.

Role: STUDY_CHAIR

University Hospital Muenster

Locations

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Centre Oscar Lambret

Lille, , France

Site Status

CHU La Timone

Marseille, , France

Site Status

MD Nicolas Andre, National Study Manager France

Marseille, , France

Site Status

CHU Nancy

Nancy, , France

Site Status

CHU Nantes

Nantes, , France

Site Status

Institut curie

Paris, , France

Site Status

Institut Gustanve Roussy

Paris, , France

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Site Status

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum Kiel

Kiel, , Germany

Site Status

Universitätsklinikum Münster

Münster, , Germany

Site Status

Klinikum Stuttgart

Stuttgart, , Germany

Site Status

Prof. Maurizio D'Incalci, National Study Manager Italy

Milan, , Italy

Site Status

Università degli Studi di Milano

Monza, , Italy

Site Status

Clinica di Oncoematologia Pediatrica

Padua, , Italy

Site Status

Università Cattolica di Roma

Rome, , Italy

Site Status

Birmingham Childrens Hospital

Birmingham, , United Kingdom

Site Status

St James's University Hospital

Leeds, , United Kingdom

Site Status

Great Ormond Street Hospital for Children

London, , United Kingdom

Site Status

Royal Manchester Childrens Hospital

Manchester, , United Kingdom

Site Status

Prof. Alan Boddy, National Study Manager UK

Newcastle upon Tyne, , United Kingdom

Site Status

Royal Victoria Infirmary, Sir James Spence Institute of Child Health

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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France Germany Italy United Kingdom

Other Identifiers

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2009-011454-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EPOC-MS-001

Identifier Type: -

Identifier Source: org_study_id