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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Glioma
• Intervention / Treatment: Drug: Doxorubicin

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Centre Oscar Lambret
  • Lyon, France
    • Centre Leon Berard
  • Marseille, France
    • CHU, Hôpital d'Enfants de la Timone
  • Paris, France
    • Institut Curie
  • Toulouse, France
    • Unité d'Hémato-Oncologie, CHU, Hôpital des enfants
  • Vandoeuvre les Nancy, France
    • CHU, Hôpital d'Enfants
  • Villejuif, France
    • Institut Gustave-Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MYOCET; 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; Other Names: MYOCET

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Pascal Chastagner, Service d'Hémato-Oncologie pédiatrique, Hôpital d'Enfants, CHU Nancy

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (Estimate): August 10, 2016

Study Record Updates

• Last Update Posted (Estimate): August 10, 2016
• Last Update Submitted That Met QC Criteria: August 5, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: 2009-017803-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No