Efficacy of Regorafenib Combined With Best Supportive Care as Maintenance Treatment in High Grade Bone Sarcomas Patients

INCLUSION CRITERIA: I1. Age ≥ 12 years at the day of consenting to the study; I2. Patients must have histologically confirmed high-grade sarcomas of bone primary localisation, including but not limited to: Osteosarcomas, Ewing sarcomas, Chondrosarcomas, Undifferenciated Pleomorphic Sarcomas (UPS), Leiomyosarcomas (LMS) and Angiosarcomas I3. Evaluable residual disease not amenable to resection after multimodal treatment principles either at diagnosis (after standard multimodal treatment based on the histological subtype) or at relapse (chemotherapy) I4. Non progressive disease (defined by the investigator according to the RECIST version 1.1 Appendix 1) at study entry; I5. Interval between the date of last anticancer treatment (chemotherapy or surgery) and the start date of regorafenib: at least 4 weeks but no longer than 2 months; I6. Life expectancy of greater than 6 months; I7. Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky ≥ 70%) (Appendix 2); I8. Adequate bone marrow and organ function defined by the following laboratory results: a. Bone marrow: i. Absolute neutrophil count ≥ 1.5 Giga/l ii. Platelets ≥ 100 Giga/l iii. Haemoglobin≥ 9 g/dl b. Hepatic function: i. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN) (≤ 5.0 × ULN for patients with liver involvement of their cancer) ii. Bilirubin ≤1.5 X ULN iii. Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN in patient with liver involvement of their cancer). If Alkaline phosphatase \> 2.5 ULN, hepatic isoenzymes 5-nucleotidase or gamma-glutamyltransferase (GGT) tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal range and/or GGT \< 1.5 x ULN. c. Renal function: i. Serum creatinine ≤ 1.5 x ULN ii. Glomerular Filtration Rate (GFR) ≥ 30 ml/min/1.73m2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula iii. Spot urine must not show ≥ 1 "+" protein in urine or the patient will require a repeat urine analysis. If repeat urinalysis shows 1 "+" protein or more, a 24-hour urine collection will be required and must show total protein excretion \< 1000 mg/24 hours d. Coagulation: International Normalized Ratio (INR)/Partial Thromboplastin Time (PTT) ≤1.5 x ULN; Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care; e. Pancreatic function: Lipase ≤ 1.5 x ULN I9. Recovery to anticancer-treatment related NCI-CTCAE v5 Grade 0 or 1 level or recovery to baseline preceding the prior treatment from any previous drug/procedure related toxicity (except alopecia, anaemia, and hypothyroidism); I10. Women of childbearing potential and male patients must agree to use adequate contraception (including at least the use of condoms) for the duration of treatment and for 7 months (210 days) in women of childbearing potential or 4 months (120 days) in men sexually active with women of childbearing potential after the last dose of regorafenib I11. Patients, and their parents when applicable, must sign and date an informed consent document indicating that they have been informed of all the pertinent aspects of the trial prior to enrolment; I12. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures; I13. Patients affiliated to the Social Security System I14. Body Surface Area (BSA) ≥ 1.30m² at the time of consenting to the study EXCLUSION CRITERIA: E1. Prior treatment with any VEGFR inhibitor (thus, any prior exposure to regorafenib, sunitinib, sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor); E2. All soft tissue sarcomas (including but not limited to soft tissue osteosarcoma), and chordomas; E3. Prior history of malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within 3 years prior to randomization; E4. Cardiovascular dysfunction defined by: * Left ventricular ejection fraction (LVEF) \< 50%, * Congestive heart failure ≥ New York Heart Association (NYHA) class 2, * Myocardial infarction \< 6 months prior to first study drug administration, * Cardiac arrhythmias requiring therapy (beta blockers or digoxin are permitted), * Unstable (angina symptoms at rest) or new-onset angina within the last 3 months prior to first study drug administration; * Uncontrolled hypertension (systolic blood pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg despite optimal treatment); * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months before the first study drug administration; E5. Major surgical procedure, open biopsy or significant traumatic injury within 28 days before the first study drug administration; E6. Ongoing infection \> Grade 2 according to NCI-CTCAE v5; E7. Known history of human immunodeficiency virus infection; Nota Bene: Subjects with diagnosed human immunodeficiency virus (HIV) are eligible to participate in the study if they meet the following criteria : 1. No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months prior to enrolment; 2. No history of AIDS-defining cancers (e.g. Kaposi's sarcoma, aggressive B-cell lymphoma and invasive cervical cancer); 3. Subjects should be on established anti-retroviral therapy for at least 4 weeks and have an HIV viral load of \< 400 copies/mL prior to enrolment; E8. Active or chronic hepatitis B or C requiring treatment with antiviral therapy; Nota Bene: Subjects with a history of hepatitis B