E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed supratentorial high-grade glioma |
Diagnosi recente di glioma di alto grado sopratentoriale. |
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E.1.1.1 | Medical condition in easily understood language |
Children with newly diagnosed brain tumor (high-grade supratentorial glioma) are eligible, provided the tumor has not spread out. |
Sono eleggibili bambini con diagnosi recente di tumore cerebrale (glioma di alto grado sopratentoriale)localizzato. |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026659 |
E.1.2 | Term | Malignant oligodendroglioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030286 |
E.1.2 | Term | Oligodendroglioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10030288 |
E.1.2 | Term | Oligodendroglioma malignant |
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 determine the benefit of the addition of bevacizumab to postoperative radiotherapy with concomitant and adjuvant TMZ. |
Determinare il beneficio dell'aggiunta di bevacizumab alla radioterapia postoperatoria con temozolomide(TMZ)concomitante e adiuvante |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy, safety and tolerability of the addition of bevacizumab to postoperative radiotherapy with concomitant and adjuvant TMZ. |
Valutare l’efficacia, la sicurezza, la tollerabilità di bevacizumab quando aggiunto alla radioterapia postoperatoria con temozolomide (TMZ) concomitante e adiuvante |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Written informed consent obtained from the patient/parents or legally acceptable representative. - Paediatric patients, age >/=3 years and <18 years - Newly diagnosed localized, supratentorial, non-brain stem WHO Grade III or IV glioma - Local histological diagnosis confirmed by a designated reference neuropathologist - Able to commence trial treatment not before 4 weeks after cranial surgery and no later tahn 6 weeks following the last major surgery - Adequate bone marrow, coagulation, liver, renal function |
- Consenso informato scritto ottenuto dal paziente/dai genitori o da un rappresentante legale accettabile. - Pazienti pediatrici: >=3 e <18 anni d’età. -HGG non troncoencefalico sopratentoriale localizzato di grado III e IV secondo OMS diagnosticato di recente. -Diagnosi istologica locale confermata da un neuropatologo di riferimento designato. -In grado di iniziare il trattamento sperimentale non prima di 4 settimane dopo intervento chirurgico craniale e non più tardi di 6 settimane dopo l’ultimo intervento importante. - Adeguata funzionalità del midollo osseo, della coagulazione, epatica e renale. |
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E.4 | Principal exclusion criteria |
- Metastatic (HGG) defined as evidence of neuraxis dessimination by MRI or positive CSF cytology. - WHO-defined Gliomatosis cerebri (multifocal HGG). - Any disease or condition that contraindicates the use of the study medication/treatment or places the patient at an unacceptable risk of experiencing treatment-related complications. - Radiological evidence of surgically related intracranial bleeding. - Prior diagnosis of a malignancy + not disease-free for 5 years. - Prior systemic anti-cancer therapy - Previous cranial irradiation |
-HGG metastatico definito come evidenza di disseminazione neurassiale attraverso RMI spinale o citologia del liquido cefalorachidiano positiva. -Gliomatosis cerebrale secondo definizione del OMS (HGG multifocale). -Qualsiasi malattia o infermità che possa controindicare l’uso del farmaco/trattamento in studio o che metta il paziente a rischio inaccettabile di complicanze dovute al trattamento. -Evidenza radiologica di sanguinamento intracraniale correlato a intervento chirurgico. -Pregressa anamnesi di tumore maligno + non libero da malattia per 5 anni. -Pregressa terapia anti-cancro sistemica. -Irradiazione craniale pregressa. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-Free Survival (EFS) – Events participating to the primary endpoint are: disease progression, disease recurrence, a second primary malignancy (other than high-grade glioma) and any other cause of mortality. |
-Sopravvivenza libera da eventi. Gli eventi che rientrano nell'end point primario sono: progressione di malattia, malattia ricorrente, un secondo tumore primario (oltre al glioma di alto grado)e qualsiasi altra causa di morte. |
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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) |
1.Overall Survival (OS) 2.Event-Free Survival (EFS) 3.Safety, feasibility and tolerability |
1.Sopravvivenza globale 2.Sovravvivenza libera da Eventi(EFS) 3.Sicurezza, fattibilità e tolleranza. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Overall and at 12 months - 6, 12 and 24 months - Over time |
1.Sopravvivenza globale e a 1 anno. 2.EFS a 6, 12 e 24 mesi 3.Nel corso dello studio |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
tolerability; late effect surveillance |
tollerabilità; sorveglianza degli effetti tardivi |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Rad+TMZ+/-BEV;seguito da 12 cicli adiuva TMZ+/-BEV |
RAD +TMZ +/- BEV; Followed by 12 Cycles Adj : TMZ+ |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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If the IDMC does not recommend that the trial terminate earlier for either futility or safety concerns, the end of the study will be the date of the final scheduled clinic visit for the last patient to complete the study or the date on which the last data point from the last patient, which is required for the OS analysis, has been received, whichever is later. |
Fine studio=data visita finale prevista per ultimo paz.che completerà lo studio oppure data in cui è stato ricevuto ultimo dato ultimo paz.richiesto x analisi OS, quale evento si verifichi più tardi, a meno che IDMC non chieda conclus.anticipata. |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |