Fight Osteosarcoma Through European Research Evolving Study Platform From Diagnosis to Relapse

REGISTRATION in FOSTER-Evolving study platfom, Part-1: Inclusion Criteria : 1. Newly diagnosed, biopsy-proven, high-grade osteosarcoma, 2. Patient considered medically fit to receive systemic treatment, 3. Planned systemic therapy according to national guidelines and age 4. Written informed consent from patients or for minor, from their parents/ legal representatives, before enrolment and any study-related procedure. 5. Affiliation to a social insurance or equivalent regimen (if required in the country). Exclusion Criteria: 1\. Low-grade osteosarcoma, parosteal or periosteal osteosarcoma, small cell osteosarcoma FOR FOSTER-CabOS RANDOMISATION (part-2) : 1. Patient with a histologically proven and confirmed high-grade osteosarcoma, according to the criteria described in the last World Health Organization (WHO) classification of Soft Tissue and Bone Tumours, after the exclusion of all potential differential diagnoses, either by local pathologists with expertise in bone sarcomas, or through centralized revision in a referral centre, according to national rules. 2. Age ≥ 4 years old (when able to swallow tablet) ; no upper age limit 3. First line systemic and local treatment of primary tumour (and metastasis when present) for localised or metastatic osteosarcoma must have been completed according to national guidelines (Mifamurtide is allowed according to centre's practices) 4. Recovery to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5 Grade 0 or 1 level or recovery to baseline health status preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anaemia, and hypothyroidism) 5. Performance status \< 2 for patient adult, or \>70 using Karnofsky or Lansky performance scores. 6. Interval between the last treatment either chemotherapy administration or surgical procedures or radiotherapy or thermoablation, (whichever occurred last) and the date of randomisation should be at least 4 weeks but no longer than 2 months; 7. Disease in complete remission or with residual persistent stable disease according to RECIST criteria before randomisation (please refer 7.3.4 for the definition of the residual persistent stable disease ) 8. Patient fit to undergo protocol treatment and follow-up 9. Adequate cardiac function: Left Ventricular Ejection Fraction (LVEF) ≥50% and/or fractional shortening (FS) \>28% at baseline as determined by echocardiography or multigated acquisition (MUGA) scan (performed only if echocardiography is not feasible) 10. Adequately controlled blood pressure (BP) with or without antihypertensive medications: BP 95th percentile for sex, age and height/length at screening (as per NHLBI (National Heart, Lung and Blood Institute) guidelines) and no change in antihypertensive medications within 1 week prior to start of treatment (C1D1). Patients aged \>18 years should have a BP ≤150/90 mmHg at screening and no change in antihypertensive therapy within 1 week prior to C1D1 11. Screening laboratory values must meet the following criteria (according to CTCAE v5) and should be obtained within 7 days prior to randomisation * Absolute neutrophil count ≥ 1 x 109/L * Platelets ≥ 100 x 109/L * Haemoglobin ≥ 8.0 g/dL (a hemoglobin of less than 8.0 g/dl is acceptable if it is corrected by growth factor or transfusion before C1D1) * Serum creatinine ≤ 1.5 x ULN or based on age/gender. If serum creatinine is greater than maximum serum creatinine for age/gender as described, then creatinine clearance (or radioisotope Glomerular Filtration Rate (GFR)) must be \>60 ml/min/1.73 m2 * Urine dipstick \< 2+ for proteinuria. Patients who have ≥2+ proteinuria on dipstick urinalysis should undergo a spot Protein/Creatinine ratio test that should be grade 2 (less or equal) per CTCAE v5.0 * No clinical evidence of nephrotic syndrome * Alanine Aminotransferase/Aspartate Aminotransferase (ALT/AST) ≤ 2.5 x Upper limit of normal (ULN) in the absence of liver metastases or ≤ 5.0 x ULN in the presence of liver metastases * Total bilirubin ≤ 1.5 x ULN (except Gilbert Syndrome: \< 3.0 mg/dL) or ≤ 5.0 x ULN in the presence of liver metastases * Alkaline phosphatase (PAL) ≤2.5 x ULN (≤5 x ULN in patient with liver involvement of their cancer). If Alkaline phosphatase \> 2.5 ULN, Gamma-Glutamyl Transferase GGT tests must be performed; GGT \< 1.5 x ULN * Lipase ≤1.5 x ULN * INR (International Normalized Ratio) /PTT (Partial Thromboplatin Time) ≤1.5 x ULN 12. Patients who are therapeutically treated with an agent such as warfarin or heparin/ Low-molecular-weight heparin (LMWH) will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. 13. Women of childbearing potential or young women of childbearing potential and who started their puberty (menarche) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of Human Chorionic Gonadotropin (HCG)) done within 7 days prior to randomisation. 14. Effective methods of contraception should be used by male and female patients and their partners during therapy, and for at least 4 months after completing therapy. Because oral contraceptives might not be considered as "effective methods of contraception", they should be used together with another method, such as a barrier method, according to age and gynaecologist advice 15. Provision of dated and signed written informed consent from patients or for minor, from their parents/ legal representatives, for the randomised trial prior to any study specific procedures, sampling and analyses.. 16. Affiliation to a social insurance or equivalent regimen (if required in the country).