Phase II pharmacokinetic study to assess the age-dependency in the clearance of doxorubicin in paediatric patients with solid tumours and leukaemia - Doxo

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2009-011454-17-DE

Enrollment

100

Registered

2009-11-17

Start date

2010-02-22

Completion date

Unknown

Last updated

2014-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute lymphoblastic leukaemia Ewing sarcoma Neuroblastoma Soft tissue sarcoma Wilms tumours

Interventions

Product Name: doxorubicin Pharmaceutical Form: INN or Proposed INN: DOXORUBICIN HYDROCHLORIDE CAS Number: 25316-40-9 Concentration unit: mg/m3 milligram(s)/cubic meter Concentration type: up to Conc

Eligibility

Sex/Gender

All

Inclusion 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 =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - prior cardiac problems

Design outcomes

Primary

Measure	Time frame
Main Objective: Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia ;Secondary Objective: - Assess interindividual, intraindividual and residual variability of PK parameters in children - Assess relationship between PK parameters and patient characteristics - Explore in a preliminary fashion genetic polymorphisms that may influence doxorubicin clearance - Evaluate the potential role of natriuretic peptides and troponin as indicators for subclinical cardiotoxicity - Provide PK data to correlate to long term toxicity, especially cardiac toxicity ;Primary end point(s): The primary endpoint is to determine if there is a difference in the doxorubicin clearance between children < 3 years 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 (Clmetabolite) and apparent volume of distribution of doxorubicinol (Vmetabolite, see chapter 11 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.	—

Measure

Time frame

Main Objective: Assess age-dependency in pharmacokinetics of doxorubicin in paediatric patients with solid tumours and leukaemia ;Secondary Objective: - Assess interindividual, intraindividual and residual variability of PK parameters in children - Assess relationship between PK parameters and patient characteristics - Explore in a preliminary fashion genetic polymorphisms that may influence doxorubicin clearance - Evaluate the potential role of natriuretic peptides and troponin as indicators for subclinical cardiotoxicity - Provide PK data to correlate to long term toxicity, especially cardiac toxicity ;Primary end point(s): The primary endpoint is to determine if there is a difference in the doxorubicin clearance between children < 3 years 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 (Clmetabolite) and apparent volume of distribution of doxorubicinol (Vmetabolite, see chapter 11 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.

—

Countries

France, Germany, United Kingdom

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026