Wilms TumorPhase 2DoxoNCT01095926
Pharmacokinetic Study of Doxorubicin in Children With Cancer
A Phase 2 study testing doxorubicin in people with Wilms Tumor and Neuroblastoma, run by University Hospital Muenster at 23 sites in 4 countries.
Trial summary
Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity . Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Wilms Tumor, Neuroblastoma, Soft Tissue Sarcoma
- What is being tested?
- doxorubicin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 23 sitesin 4 countries
- Study dates
- May 2010to May 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- prior cardiac problems
Trial locations and contacts
23 sites in 4 countries.
23 sites in 4 countries
France7 sites
Centre Oscar Lambret
Lille
CHU La Timone
Marseille
MD Nicolas Andre, National Study Manager France
Marseille
CHU Nancy
Nancy
CHU Nantes
Nantes
Institut curie
Paris
Institut Gustanve Roussy
Paris
Germany6 sites
Universitätsklinikum Essen
Essen
Universitätsklinikum Frankfurt
Frankfurt, 60690
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Universitätsklinikum Kiel
Kiel
Universitätsklinikum Münster
Münster, 48149
Klinikum Stuttgart
Stuttgart
United Kingdom6 sites
Birmingham Childrens Hospital
Birmingham
St James's University Hospital
Leeds
Great Ormond Street Hospital for Children
London
Royal Manchester Childrens Hospital
Manchester
Prof. Alan Boddy, National Study Manager UK
Newcastle upon Tyne
Royal Victoria Infirmary, Sir James Spence Institute of Child Health
Newcastle upon Tyne
Italy4 sites
Prof. Maurizio D'Incalci, National Study Manager Italy
Milan
Università degli Studi di Milano
Monza
Clinica di Oncoematologia Pediatrica
Padova
Università Cattolica di Roma
Rome
About this study
Official title: 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 .
Read the 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
- Being tested
- doxorubicin
- Keywords
- pharmacokinetic, doxorubicin, cancer, troponin, natriuretic peptide, cardiotoxicity, anthracyclines, Ewing, ALL
- Medical subject headings
- Wilms Tumor, Neuroblastoma, Sarcoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms, Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxorubicinDrug
blood sampling before, during and after doxorubicin administration
| Study group | Role | What they receive |
|---|---|---|
| Doxorubicin | Experimental | Not described Receives: Drug: doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia
Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
Measured: 24h
Secondary outcomes (4)
Assess interindividual, intraindividual and residual variability of PK parameters in children
Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
Measured: 24h
Assess relationship between PK parameters and patient characteristics
Measure doxorubicin and doxorubicinol concentration in blood plasma. Collect samples at two different doxorubicin infusions.
Measured: 24h
Explore in a preliminary fashion genetic polymorphisms that may influence doxorubicin clearance
Obtain one whole blood sample per patient, if separate consent was given.
Measured: 5 years
Evaluate the potential role of natriuretic peptides and troponin as indicators for subclinical cardiotoxicity
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.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2010 (estimated)
- Study startMay 2010
- Primary completionFeb 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wilms TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joachim Boos, MD, Prof., Study chair, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01095926
- Sponsor's protocol ID
- EPOC-MS-001
- Other IDs
- 2009-011454-17, 2009
- Acronym
- Doxo
- Status last verified
- Mar 2010
- First submitted
- 22 Mar 2010
- Last updated
- 28 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Pharmacokinetic Study to Assess the Age-dependency in the Clearance of Doxorubicin in Paediatric Patients With Solid Tumours and Leukaemia
- ClinicalTrials.gov ID
- NCT01095926
- Acronym / sponsor ID
- Doxo / EPOC-MS-001
- Keywords
- pharmacokinetic, doxorubicin, cancer, troponin, natriuretic peptide, cardiotoxicity, anthracyclines, Ewing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 30 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Analyze pharmacokinetics of doxorubicin in children with cancer. Furthermore investigate the predictive role of troponin and natriuretic peptides for anthracycline-induced cardiotoxicity .
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doxorubicin | Experimental | Drug: doxorubicin |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (1 listed)
- prior cardiac problems
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| doxorubicinblood sampling before, during and after doxorubicin administration | Drug | Doxorubicin |
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.
4 secondary outcomes
Assess interindividual, intraindividual and residual variability of PK parameters in children
Time frame: 24h
Assess relationship between PK parameters and patient characteristics
Time frame: 24h
Explore in a preliminary fashion genetic polymorphisms that may influence doxorubicin clearance
Time frame: 5 years
Evaluate the potential role of natriuretic peptides and troponin as indicators for subclinical cardiotoxicity
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joachim Boos, MD, Prof. study chair
University Hospital Muenster
23 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing doxorubicin in people with Wilms Tumor and Neuroblastoma, run by University Hospital Muenster at 23 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in France, Germany, United Kingdom, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia (time frame: 24h). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2013.