E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute lymphoblastic leukaemia Ewing Sarcoma Neuroblastoma Soft tissue sarcoma Wilms tumours |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective:
To assess age-dependency in the pharmacokinetics(rate of metabolism and elimination) of doxorubicin in paediatric patients with solid tumours or leukaemia
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E.2.2 | Secondary objectives of the trial |
•Assess between subject and within subject variability of pharmacokinetics in children •Assess relationship between pharmacokinetics and patient characteristics •Explore in a preliminary fashion genetic differences that may influence doxorubicin metabolism •Evaluation of plasma markers (natriuretic peptides and troponin) as indicators of subclinical heart toxicity •Provide data to compare to long term toxicity, especially heart toxicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. •Patient, 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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E.4 | Principal exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is to determine if there is a difference in the doxorubicin clearance between children < 3years and children 3 to < 18 years.
PK parameters including total clearance (Cl), central volume of distribution (V1), volumes of distribution for the second and third compartment (V2, V3), intercompartmental clearances (Q2, Q3), apparent clearance of doxorubicinol (Cl metabolite) and apparent volume of distribution of doxorubicinol (V metabolite, see chapter 11 of protocol for details) will be determined using population pharmacokinetics by nonlinear mixed-effects modelling(NONMEM).
Furthermore, the influence of different patient characteristics including body weight, body surface area, body mass index, age as a continuous variable, age as a categorical variable, height, sex, renal function (GFR), hepatic function (serum bilirubin, serum AST and ALT), serum albumin and tumour entity on pharmacokinetics will be assessed using NONMEM.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial in all participating countries is reached when: • the stated number of patients to be recruited is reached, • data of all patients are entered into the RDE-database and • database is locked |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |