Clinical trial NCT02861222: Myocet® in Children With Relapsed or Refractory Non-brainstem Malignant Glioma
Official title: Myocet® in Children With Relapsed or Refractory Non-brainstem Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Glioma
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2016-08-10
Enrollment: 13
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: General health evaluation
timeFrame: From day 21 post-dose
measure: 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
timeFrame: From day 21 post-dose
measure: Complete blood count (platelet included)
timeFrame: 2 times/week from day 0
measure: ALAT/ASAT measurement
timeFrame: From day 21 post-dose
measure: Bilirubin test
timeFrame: From day 21 post-dose
measure: Prothrombin test
timeFrame: From day 21 post-dose
measure: Fibrin measurement
timeFrame: From day 21 post-dose
measure: Partial thromboplastin time test
timeFrame: From day 21 post-dose
measure: Creatinine blood test
timeFrame: From day 21 post-dose
measure: Analysis of the electrolyte composition of the blood
timeFrame: From day 21 post-dose
measure: Blood urea analysis
timeFrame: From day 21 post-dose
measure: Glycemia analysis
timeFrame: From day 21 post-dose
measure: Calcemia analysis
timeFrame: From day 21 post-dose
measure: Protidaemia analysis
timeFrame: From day 21 post-dose
measure: Normality of ECG
timeFrame: From day 21 post-dose
measure: Echocardiography with analysis of ventricular ejection and shortening fractions
timeFrame: From day 21 post-dose
Secondary outcomes:
measure: Measure of initial tumors with MRI
timeFrame: from day 42, after each 2 treatments
measure: Antitumoral activity (radiological criteria of SIOP protocol)
timeFrame: from day 42, after each 2 treatments
measure: Plasma measurement of free doxorubicin
timeFrame: 0, 2, 5, 11, 47, 71 hours after the first dose
measure: Plasma measurement of encapsulated doxorubicin
timeFrame: 0, 2, 5, 11, 47, 71 hours after the first dose
measure: Plasma measurement of doxorubicinol
timeFrame: 0, 2, 5, 11, 47, 71 hours after the first dose
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: CHU, Hôpital d'Enfants de la Timone
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Unité d'Hémato-Oncologie, CHU, Hôpital des enfants
city: Vandoeuvre les Nancy
country: France
facility: CHU, Hôpital d'Enfants
city: Villejuif
country: France
facility: Institut Gustave-Roussy
Study officials:
affiliation: Service d'Hémato-Oncologie pédiatrique, Hôpital d'Enfants, CHU Nancy
name: Pascal Chastagner
role: PRINCIPAL_INVESTIGATOR
References: