AsiDNA Children, Adolescents and Young Adults

Inclusion Criteria:

1. Written informed consent from patient (depending on age) and/or parents or legal guardian;
2. Patient must be ≥ 12 months and \< 25 years of age at the time of enrolment on the study;
3. Recurrent high-grade glioma (HGG), including diffuse midline glioma (DMG) and non-DMG, based on RAPNO criteria confirmed by central radiological review, with or without histology if biopsy performed prior to inclusion;
4. Available tumour material, at least paraffin embedded and/or also frozen material;
5. For DMG and non-DMG HGG, prior radiation dose prescribed ≤ 60 Gy, completed at least 6 months prior to inclusion, with stable disease;
6. Maximum cumulative radiation dose to optic chiasm and optic nerve \< 56 Gy and \< 54 Gy to upper cervical spine (at level C1);
7. Life expectancy \> 2 months at Screening;
8. Patient must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 50 % , not taking into account neurological deficit;
9. No significant abnormality on laboratory tests at Screening, including:

   1. Haemoglobin \> 9 g/dL;
   2. Neutrophils \> 1.0 x 109/L;
   3. Platelets \> 100 x 109/L;
   4. Total bilirubin \< 1.5 x ULN;
   5. AST and ALT\< 2.5 x ULN;
   6. Serum creatinine \< 1.5 x ULN for age;
   7. Normal coagulation tests.
10. No organ toxicity \> grade 2 according to NCI CTCAE version 5.0 classification, notably cardiovascular, pulmonary or renal diseases, including congenital QT prolongation syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite appropriate treatment, interstitial pulmonary disease, pulmonary hypertension;
11. Negative serum pregnancy test for women of child-bearing potential, and highly effective birth control method for male and female patients of reproductive potential;
12. Patients covered by social security or health insurance in compliance with the national legislation relating to biomedical research.

Exclusion Criteria:

5\. Prior radiation dose prescribed \> 60 Gy; 6. Massive intra-tumour haemorrhage; 7. Pseudoprogression (including after central review); 8. Metastatic relapse; 9. Other anticancer treatment, on-going or within less than 4 weeks prior to inclusion; 10. Prior or concurrent malignant disease, other than HGG, diagnosed or treated within 5 years prior to inclusion; patients with CMMRD are eligible; 11. Uncontrolled intercurrent disease or active infection; 12. Concomitant disease or other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study; 13. Patients unable to comply with the protocol for any reason; 14. Organ toxicity \> grade 2 according to NCI CTCAE version 5.0 classification, notably cardiovascular, pulmonary or renal diseases, including congenital QT prolongation syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite appropriate treatment, interstitial pulmonary disease, pulmonary hypertension 15. Breastfeeding or pregnancy