E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glioblastoma multiforme, diffuse intrisic pontine glioma, diffuse glioma of the brain stem and spinal cord, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma |
Glioblastoma multiforme, glioma intrinseco diffuso pontino, gliomi diffusi del tronco encefalico, spinali e talamici bilaterali, gliomatosis cerebri e astrocitomi anaplastici |
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E.1.1.1 | Medical condition in easily understood language |
High-grade diffuse gliomas |
Neoplasie cerebrali diffuse |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018338 |
E.1.2 | Term | Glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess safety and tolerability of continuous infusion of doxorubicin when added to standard therapy in pediatric and adult patients with newly diagnosed glioblastoma multiforme, diffuse intrisic pontine glioma, diffuse glioma of the brain stem and spinal cord, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma |
Valutare la sicurezza e la tollerabilit¿ della somministrazione prolungata di doxorubicina in combinazione con il trattamento standard nella terapia di prima linea in pazienti pediatrici e giovani adulti affetti da GBM, DIPG, gliomi diffusi del tronco encefalico, spinali e talamici bilaterali, gliomatosis cerebri e astrocitomi anaplastici. |
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E.2.2 | Secondary objectives of the trial |
To evaluate efficacy of the treatment through assessment of event free survival (EFS) defined as tumor progression, tumor recurrence and death attributable to any cause, and overall survival (OS). |
Valutare l¿efficacia del trattamento mediante determinazione della sopravvivenza libera da eventi (EFS), quali progressione di malattia, comparsa di recidiva e mortalit¿ per qualsiasi causa, e sopravvivenza globale (OS).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males and females patients, aged >3 years and < 30 years; Histologically confirmed newly diagnosed glioblastoma multiforme, diffuse intrisic pontine glioma, diffuse glioma of the brain stem and spinal cord, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma; Patients undergone either surgery or biopsy only; No prior chemotherapy and/or radiotherapy; Life expectancy = 4 weeks; Karnofsky/Lansky = 40 %; Written informed consent obtained from the patient/parents or legal representative; Adequate hematological function (leucocyte = 2.0 x 10^9/l - Hemoglobin = 10 g/dl - platelet = 50 x 10^9 /l); Adequate liver function (total bilirubin = 2.5 x ULN - ALT/AST = 5.0 x ULN); Adequate renal function (serum creatinine = 1.5 x ULN); Availability to trial treatment and ability to be compliant with the protocol
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Pazienti con glioblastoma multiforme, glioma intrinseco diffuso pontino, gliomi diffusi del tronco encefalico, spinali e talamici bilaterali, gliomatosis cerebri e astrocitomi anaplastici di prima diagnosi non precedentemente trattati (con chemio-radioterapia) o trattati solo chirurgicamente; Maschi e femmine di età compresa fra i 3 e i 30 anni; Aspettativa di vita = 4 settimane; Karnofsky/Lansky = 40 %; Funzione ematologica adeguata: - Conta assoluta dei leucociti = 2.0 x 10^9/l - Emoglobina = 10 g/dl - Conta delle piastrine = 50 x 10^9 /l Funzione epatica adeguata: - Bilirubina totale = 2.5 x ULN - ALT/AST = 5.0 x ULN Funzione renale adeguata: - Creatinina sierica = 1.5 x ULN Consenso informato scritto da parte del paziente, dei genitori o dei tutori legali; Disponibilità del paziente durante il trattamento e capacità di attenersi al protocollo;
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E.4 | Principal exclusion criteria |
Any disease or condition that contraindicates the use of the study treatment (es. serious mental retardation, brain palsy, congenital syndrome, cardiomyopathy) Prior anti-cancer therapy Pregnancy or breastfeeding Non adequate contraception |
Evidenza di qualsiasi altra malattia o condizione gravi che rappresentino una controindicazione alla terapia in studio (e.g. grave ritardo mentale, grave paralisi cerebrale, gravi sindromi congenite, cardiopatie) Esecuzione di un ciclo di chemioterapia di 1° linea contemporaneamente all’inizio dello studio; Concomitante partecipazione ad altri progetti di ricerca Stato di gravidanza o allattamento Utilizzo di metodi contraccettivi inadeguati sia da parte di pazienti di sesso femminile che maschile
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary safety end points: -Time to early discontinuation of the experimental treatment (doxorubicin) -Percentage of subjects with SAE leading to withdrawal from the study -Percentage of SAE -Mortality due to adverse events -Rate of early suspension of experimental treatment with doxorubicin |
Endpoint primario di sicurezza è definito come: - Tempo alla sospensione precoce del trattamento sperimentale con Doxorubicina - Percentuale di soggetti con SAE che determinano il ritiro dallo studio - Percentuale di SAE - Mortalità per eventi avversi - Proporzione di sospensioni precoci del trattamento sperimentale con Doxorubicina |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy end points: -Event free survival (EFS) defined as time frame between the date of enrolment and the earliest occurence of anyone of the following: progression based on RECIST 1.1 criteria; tumor recurrence; death to any cause. -Overall survival (OS) defined as time frame between the date of the enrolment and the death to any cause -Progression free survival (PFS) defined as time frame between the date of the enrolment and the date tumor progression based on RECIST 1.1 criteria -Rate of treatment response (CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease) based on RECIST 1.1 criteria |
End point secondari di efficacia: -Sopravvivenza libera da eventi (EFS) calcolata come il tempo tra la data di arruolamento e la data di comparsa di uno dei seguenti eventi: progressione di malattia stabilita secondo i criteri RECIST 1.1; comparsa di recidiva; mortalit¿ per qualsiasi causa. -Sopravvivenza globale (OS) definita come il tempo tra la data di arruolamento e la data di decesso per qualsiasi causa. -Sopravvivenza libera da progressione di malattia (PFS) definita come il tempo tra la data di arruolamento e la data di progressione secondo i criteri RECIST 1.1 -Proporzione di risposta al trattamento (CR, risposta completa; PR, risposta parziale; SD, malattia stabile; PD, progressione di malattia) secondo i criteri RECIST 1.1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Every 2 months |
Ogni 2 mesi |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the follow-up of the last subject |
La fine dello studio ¿ definita come l'ultima visita di follow-up per l'ultimo paziente arruolato. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 56 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 56 |
E.8.9.2 | In all countries concerned by the trial days | 0 |