Axitinib and Oral Metronomic Etoposide for Pediatric Children and AYA Refractory/Relapsing Medulloblastoma and Ependymoma

Inclusion Criteria: * Histologically proven diagnosis of ependymoma or medulloblastoma * Methyloma classification performed or available material for methyloma analysis * Confirmed progressive or refractory disease despite standard therapy, or for which no effective standard therapy exists * Male and female subjects with \> 4 to ≤ 25 years of age at inclusion * Weight \> 20 kg * Evaluable target lesion(s) according to RAPNO * Performance status: Karnofsky performance status (for patients \>12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 70%. Patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score * Life expectancy ≥ 3 months * No known allergy to any of the compounds in the experimental treatment * Able to take oral treatments * Adequate organ function: Hematologic criteria * Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 (unsupported) * Platelet count ≥ 100,000/mm3 (unsupported) * Hemoglobin ≥ 8.0 g/dL (transfusion is allowed) Cardiac function * Shortening fraction (SF) \>29% and left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy). Renal and hepatic function * Serum creatinine \< 1.5 x upper limit of normal (ULN) for age * Total bilirubin \< 1.5 x ULN * Alanine aminotransferase (ALT)/ Aspartate aminotransferase (AST)/ \< 2.5 x ULN * Able to comply with scheduled follow-up and with management of toxicity. * Females of child bearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment. * Sexually active patients must agree to use adequate and appropriate contraception (in accordance with Clinical Trials Facilitation and Coordination Group (CTFG) recommendations) while on study drug and for 6 months after stopping the study drug. * Patient able to comfortably swallow capsules. * Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines. * Patient affiliated to a social security regimen or beneficiary of the same according to local requirements. Non-inclusion Criteria * Chemotherapy within 21 days of day 1 from the start of study treatment. This period can be shortened in the case of treatment with vincristine (2 weeks) and extended to 6 weeks in the case of treatment with nitrosureas. The period is set to 5 half-lives in the case of targeted therapies or metronomic chemotherapy. The period is set to 2 weeks after bevacizumab administration. Evidence of \> Grade 1 recent CNS hemorrhage on the baseline MRI or scan. * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). * Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening). * Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection. * Presence of any NCI-CTCAE v5 grade ≥ 2 treatment-related extra-hematological toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy. * Known congenital immunodeficiency. * Radiotherapy within the 2 months preceding D1 of the start of study treatment. Palliative RT on a non-target lesion is allowed up to 1 weeks before beginning of treatment. * Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered. * Bleeding disorder. * Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening). * Known hypersensitivity to any study drug or component of the formulation. * Absence of effective contraception in patients of childbearing age (see appendix 3) * Pregnant or nursing (lactating) females. * Patients with galactose intolerance, lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases). * Severe infections requiring parenteral antibiotic therapy. * Inability to undergo medical monitoring of the trial for geographic, social or psychological reasons.