Malignant Glioma
Conditions
Brief summary
The purpose of this study is to determine the toxicity and tolerance of Myocet® in children and adolescents with refractory or relapsed malignant glioma, with a dose diminished of 20% of the dose recommended for adults and a dose recommended for adults, administered in single dose in 1-hour perfusion each 21 days. Other purposes are to determine the recommended dose of Myocet and to assess the response to drug. Pharmacokinetics of doxorubicin (free and encapsulated forms) and its metabolite doxorubicinol during 72 hours after Myocet administration will also be studied.
Interventions
DRUGDoxorubicin
Sponsors
Central Hospital, Nancy, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Patients having received at least one cycle of chemotherapy after radiotherapy * Patients having grade III or IV (WHO) glioma, not localized in brainstem * Tumor measurable with magnetic resonance imaging * Absence of other concomitant anti-cancer treatments * Absence of chemotherapy for 4 weeks; 6 weeks if nitrosourea * Good general health and nutritional status according to NCI-CTC scale (version 3) (appendix 6) * Lansky score \> 50% or Karnofsky \> 50 in children older than 12 years * Absence of organ toxicity (grade \> 2 according to NCI-CTC criteria (version 3) * Hematology: polynuclear neutrophil count \> 1.0 x 109/l * Hematology: platelet count \> 100 x 109/l * Liver function: bilirubinemia \< 1.5 normal value * Liver function: ASAT and ALAT levels \< 2.5 normal values * Liver function: prothrombin level \> 70% * Liver function: fibrinogen \> 1.5 g/l * Renal function: creatinemia \< 1.5 normal value/age * Cardiac function: EF \> 60% and/or SF \> 30% * Signature of informed consent by patient if adolescent, by 2 parents or legal guardian if minor patient * For patients with childbearing potential, a contraceptive method is compulsory. This contraception must be continued 6 months after Myocet treatment end * For patients with childbearing potential, negative pregnancy test (betahCG test)
Exclusion criteria
* Non compliance with eligibility criteria * Severe or life-threatening infection * Non controlled evolutive or symptomatic intracranial hypertension * History of Myocet treatment, but patients could be treated with anthracyclines if cardiac function is normal * Hypersensibility to the active substance, to premixtures or one of excipients * Pregnancy and breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Echocardiography with analysis of ventricular ejection and shortening fractions | From day 21 post-dose | — |
| Blood urea analysis | From day 21 post-dose | — |
| Glycemia analysis | From day 21 post-dose | — |
| Calcemia analysis | From day 21 post-dose | — |
| Protidaemia analysis | From day 21 post-dose | — |
| Normality of ECG | From day 21 post-dose | — |
| General health evaluation | From day 21 post-dose | NCI-CTC scale, version 3, appendix 6 |
| Changes in neurological condition related to the tumor (motor deficit, sensory deficit, cranial nerves pairs defect, cerebellar syndrome, vertebrobasilar defect, pyramidal tract syndrome) assessed during clinical examination | From day 21 post-dose | — |
| Complete blood count (platelet included) | 2 times/week from day 0 | — |
| ALAT/ASAT measurement | From day 21 post-dose | — |
| Bilirubin test | From day 21 post-dose | — |
| Prothrombin test | From day 21 post-dose | — |
| Fibrin measurement | From day 21 post-dose | — |
| Partial thromboplastin time test | From day 21 post-dose | — |
| Creatinine blood test | From day 21 post-dose | — |
| Analysis of the electrolyte composition of the blood | From day 21 post-dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Antitumoral activity (radiological criteria of SIOP protocol) | from day 42, after each 2 treatments |
| Plasma measurement of free doxorubicin | 0, 2, 5, 11, 47, 71 hours after the first dose |
| Plasma measurement of encapsulated doxorubicin | 0, 2, 5, 11, 47, 71 hours after the first dose |
| Plasma measurement of doxorubicinol | 0, 2, 5, 11, 47, 71 hours after the first dose |
| Measure of initial tumors with MRI | from day 42, after each 2 treatments |
Countries
France
Outcome results
None listed