A Study of Avastin (Bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma

Inclusion Criteria:

• Paediatric patients, age >/=6 months and <18 years
• Written informed consent obtained from the patient/parents or legally acceptable representative
• 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 than 6 weeks following the last major surgery
• Adequate bone marrow, coagulation, liver, renal function

Young Patient Cohort

• Written informed consent obtained from parents or legal representative
• Age at enrolment: from >/= 6 months to < 3 years of age
• Progressive or relapsed metastatic or localised, supra- or infratentorial, non-brain stem WHO Grade III or IV glioma (local pathology confirmation made either at initial diagnosis or at relapse)
• Availability of a baseline magnetic resonance imaging (MRI) performed according to imaging guidelines
• Adequate organ function (bone marrow, coagulation, liver, kidney)

Exclusion Criteria:

• Metastatic (HGG) defined as evidence of neuraxis dissemination 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

Young Patient Cohort

• WHO-defined Gliomatosis cerebri (multifocal high-grade glioma)
• Newly diagnosed high-grade glioma below the age of 3 years
• Relapsed HGG below the age of 6 months or above the age of 3 years regardless of the age at first onset
• Indication for concomitant cranial irradiation, regardless of age
• Any disease or condition that contraindicates the use of the study medication/treatment or places the child at an unacceptable risk of experiencing treatment-related complications
• Any specific contraindication to MRI
• Radiological evidence of surgically related intracranial bleeding
• Any bleeding diathesis
• Any clinically significant cardiovascular disease
• Unresolved infection
• An active peptic ulcer
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to start of treatment or the anticipation of the need for major (elective) surgery during the course of the study treatment
• Minor surgical procedures within 2 days prior to the start of treatment (central venous access device including peripherally inserted central line)
• Non-healing surgical wound
• A bone fracture that has not satisfactorily healed
• Prior diagnosis of a malignancy and not disease-free for 5 years