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

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 or C who have normal alanine aminotransferase (ALT) and are hepatitis B surface antigen negative and/or have undetectable HCV RNA are eligible
• •E9. Dehydration according to NCI-CTCAE v5 Grade \>1;
• •E10. 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);
• •E11. Patients with seizure disorder requiring medication;
• •E12. Concurrent enrolment in another clinical trial in which investigational therapies are administered;
• •E13. Known hypersensitivity to the active substance or to any of the excipients;
• •E14. Pregnant women, women who are likely to become pregnant or are breast-feeding. Women of childbearing potential must have a negative serum β-Human Chorionic Gonadotropin (HCG) pregnancy test within 7 days prior randomization;
• •E15. 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;
• •E16. Patients with history of non-compliance to medical regimens or unwilling or unable to comply with the protocol;
• •E17. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent;
• •E18. Non-healing wound, non-healing ulcer, or non-healing bone fracture;
• •E19. Patients with evidence or history of any bleeding diathesis, irrespective of severity;
• •E20. Any haemorrhage or bleeding event ≥ CTCAE v5 Grade 3 within 4 weeks prior to the first study drug administration;
• •E21. 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;
• •E22. Patients using prohibited concomitant and/or concurrent medications (see section "Prohibited concomitant/concurrent treatments);
• •E23. Patients under tutorship or curatorship.