E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed high-grade glioma |
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E.1.1.1 | Medical condition in easily understood language |
Children with newly diagnosed brain tumor (high-grade glioma) are eligible, provided the tumor has not spread out. |
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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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002226 |
E.1.2 | Term | Anaplastic ependymoma |
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 | 19.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027744 |
E.1.2 | Term | Mixed astrocytoma-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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065443 |
E.1.2 | Term | Malignant 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 | 19.1 |
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 | 19.1 |
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.1.3 | 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 in terms of EFS of the addition of bevacizumab to postoperative radiotherapy with concomitant and adjuvant TMZ. |
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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. |
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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- or infratentorial cerebellar or peduncular, WHO Grade III or IV gliomas - Local histological diagnosis confirmed by a designated central reference neuropathologist - Availability of a baseline MRI performed according to imaging guidelines - Able to commence trial treatment not before 4 weeks after cranial surgery and no later than 6 weeks following the last major surgery - Adequate bone marrow, coagulation, liver, renal function |
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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 and disease-free for 5 years - Prior systemic anti-cancer therapy - Previous cranial irradiation |
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-free Survival (EFS) as assessed by the central radiology review committee |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after last evaluable patients has been randomized |
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E.5.2 | Secondary end point(s) |
1. Overall Survival (OS) and 1 year survival rate 2. 6 month and 1 year EFS rates 3. EFS as assessed by the investigates 4. Overall Response Rate as assessed by central radiology committee 5. Functional changes in tumour on diffusion/perfusion MRI imaging 6. Health status as measured by the Health Utility Index (HUI) 7. Neuro-psychological function as measured by the Wechsler scale 8. Safety, feasibility and tolerability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at the time of primary endpoint analysis (interim OS) and 3 years after the last patient has been randomised (final OS) 2. at the time of primary endpoint analysis 3. at the time of primary endpoint analysis 4. at the time of primary endpoint analysis 5. at the time of primary endpoint analysis 6. at the time of primary endpoint analysis 7. at the time of primary endpoint analysis 8. Over time by the IDMC, at the time of primary endpoint analysis, and final OS analysis |
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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 |
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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; Followed by 12 Cycles Adj : TMZ+/- Bev |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Hungary |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
United Kingdom |
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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. |
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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 |