Patient description: The patient is a 60 year old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is worsening. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions are detected in the head and face. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. His serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). His family history is only significant for hypertension in his mother and DM type 2 in his father. The diagnosis of Paget's Disease of Bone was confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 16.0-999.0,  Bone Sarcoma Osteosarcoma  I1. Age ≥ 16 years at the day of consenting to the study; I2. Patients must have histologically confirmed diagnosis of primary bone sarcoma of one of the following histotypes OS (conventional-intramedullary/central high grade, small cell, telangiectatic or high-grade surface OS) Bone sarcomas other than Ewing sarcoma, chondrosarcoma and chordoma; I3. Availability of archival Formalin-Fixed Paraffin Embedded (FFPE) block. I4. Prior treatment for localized or metastatic disease for bone sarcoma must have been completed. It should Neoadjuvant chemotherapy with documented assessment of histological response Local procedure: Surgery (or radiotherapy if tumour is unresectable) Adjuvant chemotherapy (Nota Bene: patients with histotype different from OS may not have received adjuvant treatment) For OS, excepted from head and neck, neoadjuvant and/or adjuvant chemotherapy should methotrexate-based regimen for patients < 18 years old or anthracycline and cisplatin-based regimen for patients ≥ 18 years old. For head and neck OS, neoadjuvant and/or adjuvant chemotherapy should adriamycin, cisplatin or ifosfamide-based regimen. For non-OS, neoadjuvant and/or adjuvant chemotherapy should adriamycin and/or cisplatin-based regimen. I5. Recovery to 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); I6. Interval between the last chemotherapy administration and the date of randomisation : at least 4 weeks but no longer than 2 months; I7. Confirmed complete remission or no evidence of disease (for metastatic disease); Patients with pulmonary micro nodules can be included provided they do not meet the following At least one lung nodule of 10 mm or more And/or at least two nodules well limited between 6-9 mm And/or at least 5 nodules well limited of 5 mm or less All the other situations will be considered as doubtful lesions except in case of metastatic disease confirmed during the lung surgery of the residual lung lesions after pre-operative chemotherapy. If no other metastatic localisation is detected at the initial staging, the patient will be considered as localised disease and eligible for randomisation. I8. Life expectancy of greater than 12 months; I9. Karnofsky Performance status ≥ 70 (patients younger than 18-year old) or Eastern Cooperative Oncology Group (ECOG) performance status < 2 (adult patients) (Cf. appendix 2); I10. Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation  Absolute neutrophil count ≥ 1.5 Giga/l   E1. Prior treatment with any VEGFR inhibitor (thus, any prior exposure to sunitinib, sorafenib, pazopanib, bevacizumab, or other VEGFR inhibitor); E2. All soft tissue sarcomas (including but not limited to soft tissue osteosarcoma and Ewing soft tissue sarcoma), and Ewing sarcoma, chondrosarcoma and chordoma; E3. Prior history of other 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 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 (begun within the last 3 months prior to first study drug administration); E5. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg despite optimal treatment); E6. 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; E7. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before the first study drug administration; E8. Ongoing infection > Grade 2 according to NCI-CTCAE v5; E9. Known history of human immunodeficiency virus (HIV) infection; E10. Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy; E11. Dehydration according to NCI-CTCAE v5 Grade > 1; E12. Difficulties to swallow oral medication and/or any mal-absorption condition and/or any Gastrointestinal (GI) disease that may significantly alter the absorption of regorafenib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection); E13. Patients with seizure disorder requiring medication; E14. Concurrent enrolment in another clinical trial in which investigational therapies are administered; E15. Known hypersensitivity to the active substance or to any of the excipients; E16. Pregnant women, women who are likely to become pregnant or are breast-feeding; E17. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial; E18. Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol; E19. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent; E20. Non-healing wound, non-healing ulcer, or non-healing bone fracture; E21. Patients with evidence or history of any bleeding diathesis, irrespective of severity; E22. Any haemorrhage or bleeding event ≥ NCI-CTCAE v5 Grade 3 within 4 weeks prior to the first study drug administration; E23. Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results; E24. Patients using prohibited concomitant and/or concurrent medications (see section "Prohibited concomitant/concurrent treatments"); E25. Patients under tutorship or curatorship