Myocet® in Children With Relapsed or Refractory Non-brainstem Malignant Glioma

Study Overview
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Brief Summary
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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.

Official Title
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Myocet® in Children With Relapsed or Refractory Non-brainstem Malignant Glioma

Conditions
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Malignant Glioma

Intervention / Treatment
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* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MYOCET<br>2 treatments of doxorubicin are administered at 60 mg/m²/day or 75 mg/m²/day in single dose in 1-hour perfusion each 21 days. A maximum of 6 treatments/patient is administered. | Drug: Doxorubicin<br> <br> * Other names: MYOCET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General health evaluation | NCI-CTC scale, version 3, appendix 6 | From day 21 post-dose | 
| 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 | 
| 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 | 
| Echocardiography with analysis of ventricular ejection and shortening fractions |  | From day 21 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of initial tumors with MRI |  | from day 42, after each 2 treatments | 
| 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 |