An International Clinical Program for the Diagnosis and Treatment of Children With Ependymoma

After Initial surgery, patients will be enrolled in one of 3 different interventional strata where they will be offered a set of therapeutic interventions based on the outcome of the intervention (no measurable residue vs residual inoperable disease), their age and/or their eligibility /suitability to receive radiotherapy. Patients with centrally and histologically confirmed intracranial ependymoma meeting the following criteria will be enrolled into one of interventional stratum: * Age \< 22 years old at diagnosis * Newly diagnosed intracranial ependymoma of WHO grade II-III confirmed by central pathological review * Post-menarchal female not pregnant or nursing (breast feeding) and with a negative beta-HCG pregnancy test prior to commencing the trial * Males and females of reproductive age and childbearing potential with effective contraception for the duration of their treatment and 6 months after the completion of their treatment * No contraindication to the use if one of the study drugs proposed by the protocol * Patients and/or their parents or legal guardians willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedure * No co-existent unrelated disease at the time of study entry that would render the patient unable to receive chemotherapy * No signs of infection. Common inclusion criteria for Strata 1 and 2: * Age \> 12 months and \< 22 years at time of study entry * No metastasis on spinal MRI and on CSF cytology assessments * No previous radiotherapy * No previous chemotherapy (except steroids) * No medical contraindication to radiotherapy and chemotherapy * Adequate bone marrow, liver and renal functions Specific inclusion criteria for Stratum 1: • No residual measurable ependymoma based on the central neuroradiological review (R0-1-2) Specific inclusion criteria for Stratum 2: • Residual non reoperable measurable ependymoma based on the central neuroradiological review (R3-4) Inclusion criteria for Stratum 3: * Children younger than 12 months at time of entry to study or any children ineligible to receive radiotherapy due to age at diagnosis, tumour location or clinician / parent decision and according to national criteria * Adequate bone marrow, liver and renal functions * No previous chemotherapy and radiotherapy * No contraindication to chemotherapy Patients that do not fulfill the inclusion criteria of one of the interventional strata will be enrolled and followed up into an observational study and descriptive analysis will be performed. EXCLUSION CRITERIA for all interventional strata: * Tumour entity other than primary intracranial ependymoma * Primary diagnosis predating the opening of SIOP Ependymoma II * Patients with WHO grade I ependymoma including ependymoma variants: myxopapillary ependymomas and subependymomas,patients with spinal cord location of the primary tumour * Participation within a different trial for treatment of ependymoma * Contraindication to one of the IMP used according to the SmPCs * Concurrent treatment with any anti-tumour agents * Inability to tolerate chemotherapy * Unable to tolerate intravenous hydration * Pre-existing mucositis, peptic ulcer, inflammatory bowel disease ascites, or pleural effusion. Strata 1 and 2: * Ineligible to receive radiotherapy * Patient for whom imaging remains RX despite all effort to clarify the MRI conclusion Stratum 3: * Pre-existing severe hepatic and/or renal damage * Family history of severe epilepsy * Presence of previously undiagnosed mitochondrial disorder detected by screening as part of trial * Elevated blood ammonium and lactate level ≥ 1.5 x upper limit of the normal