Phase 2 open label randomized study of radiotherapy, concomitant nimotuzumab and vinorelbine and re-irradiation at relapse versus radiotherapy and multiple elective radiotherapy courses with concomitant vinorelbine and nimotuzumab for newly diagnosed childhood and adolescence diffuse intrinsic pontine glioma (DIPG).

Prior treatment

• Pre-treatment with radio or chemotherapy

Other illness

• Metastatic disease as shown by MRI

Other

• Patients below 2 years or over 21
• Neurofibromatosis 1
• Non-typical imaging
• Symptoms duration over 6 months, Lansky/Karnowski scores below 40%
• Organ dysfunction, pregnancy or breast-feeding
• Absence of parents, patient or tutor consent
• Not central review diagnosis of diffuse midline glioma histone H3, K27 mutated

• Patients from 2 to 21 years old will be eligible
• No previous treatment consented apart from steroids
• Strict eligibility criteria will radiologically-verified DIPG (an intrinsic, pontine-based infiltrative lesion hypointense on T1- and hyperintense on T2-weighted sequences, involving at least 2/3 of the pons) [Hargrave]
• Symptoms lasting less than 6 months, life expectancy ≥4 weeks; Karnowski/Lansky performance status ≥ 40 %
• No organ dysfunction; no pregnancy or breast-feeding
• Patients undergo baseline cranial MRI with gadolinium, to be repeated if treatment begins more than 2 weeks; spinal MRI due to the occurrence of metastatic cases at diagnosis will also be mandatory
• Written and signed informed consent from parents or legal guardians will be obtained before starting the treatment
• For diffuse midline glioma observational arm, central reviewed pathology of the disease according to standard Italian procedure, i.e. referral to the Neuropathology at Sapienza University in Rome