Different pediatric cancers such as malignant glioma and also relapsed or refractory neuroblastoma, rhabdomyosarcoma, medulloblastoma, and Ewing sarcoma, for which treatment with the cytotoxic temozolomide is recommended as per treatment guidelines. MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA versio
Conditions
Sponsors
ORPHELIA Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Paediatric patients in need of temozolomide (all indications with 5-day treatment per 21- or 28-day cycle). • Male and female patients aged 1 to less than 18 years • Patients who have signed the informed consent or for which one, both parents or legal guardian (depending on local legislation) have signed the informed consent. • Patients having records of coverage by a health insurance • Life expectancy = 3 months • Adequate haematological function: o haemoglobin = 80 g/L (transfusion support authorized) o neutrophil count = 1.0 x 10e9 cells/L o platelet count = 100 x 10e9 cells/L (without transfusion support) o in case of bone marrow involvement: neutrophils = 0.5 x 10e9 cells/L and platelets =75 x 10e9 cells/L • Adequate renal function: o Creatine clearance = 60 mL/min.1.73m² according to the Schwartz formula [1] or its modified form [2] • Adequate hepatic function: o bilirubin =1.5 x ULN o AST and ALT = 2.5 x ULN (AST, ALT 5xULN in case of liver metastases) • Lansky Score = 70% Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients who are co-administrated at day one with sodium valproate as it decreases the clearance of temozolomide • Patients with (naso)gastric tube administration of temozolomide during first cycle of treatment • Patients already enrolled in studies investigating temozolomide or other investigational new drugs • A post-menarche female with a positive blood/urine pregnancy test at inclusion • Known contraindication or hypersensitivity to temozolomide or any chemically close substance
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate pharmacokinetic parameters of the oral suspension of temozolomide in the paediatric population aged 1 year and over;Secondary Objective: Evaluate the safety of the oral suspension of temozolomide, Evaluate the acceptability of the oral suspension of temozolomide. Describe the activity of the oral suspension of temozolomide over the course of a 6-month-treatment period (complete or partial response, disease progression, stable disease) according to the standard follow up exams and tests recommended for each indication ;Primary end point(s): Primary endpoint: Investigated PK parameters will be TMZ apparent clearance (CL/F), distribution volume (V/F) and absorption rate constant (Ka). These PK parameters will be used to derive key estimates of exposure such as TMZ area under the curve between 2 intakes (AUC0-t) and, if feasible, maximum concentration (Cmax) for each included subject and elimination half-life (t1/2), and the total AUC0-8. Population PK parameters will be estimated by a population analysis performed with NONMEM (7.4). Individual Bayesian estimates of the PK parameters will be used to calculate individual AUC24, Cmax, and t1/2.;Timepoint(s) of evaluation of this end point: A total of 6 blood samples of 1 ml will be drawn per patient in a single daytime hospitalisation. Blood samples will be collected in prechilled K2-EDTA tubes prior to Kimozo administration and at 0.10-0.20 (6-12 min), 0.33-0.66 (20-40 min), 0.75-1.5 (45-90 min), 2.0-3.0 and 6.0-8.0 hours post-dose. The administered dose and exact time for each sample will be recorded. Should a patient be naïve to any prior treatment with TMZ, the pre-treatment sample is not necessary. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • Acceptability The acceptability of the oral suspension of temozolomide will be scored with a standardized assessment tool: CAST - ClinSearch Acceptability Score Test. This tool measures 9 observational drivers of medicine acceptability. • Safety All Safety events will be collected throughout the study, including buccal tolerance • Activity The clinical activity of the oral suspension of temozolomide during the compassionate use period will be described according to the standard follow-up exams and tests (i.e. complete or partial response, disease progression, stable disease);Timepoint(s) of evaluation of this end point: Secondary endpoints: • Acceptability A paper diary will be filled-in to assess palatability/acceptability of the oral suspension of temozolomide. • Safety Safety events recorded by the caregiver in the patient diary will be medically controlled on a monthly basis by the principal investigator. Safety follow-up during the 1st cycle : 21 or 28 days, including buccal tolerance at day 5 and until day 21 or 28 Safety follow-up during the compassionate-use period for 5 potential additional treatment cycles. • Activity The clinical activity during the compassionate use period will be assessed when planned for the standard follow-up exams and tests | — |
Countries
France, Germany, Netherlands, Spain, United Kingdom
Contacts
Public ContactContact
ORPHELIA Pharma
Outcome results
None listed