REGO_INTER-EWING-1: This study is testing the feasibility of treatment with targeted therapy (called regorafenib) with conventional chemotherapy in people with newly diagnosed, multimetastatic Ewing sarcomaPhase Ib Study of the Combination of Regorafenib With Conventional Chemotherapy for the Treatment of Newly Diagnosed Patients With Multimetastatic Ewing Sarcoma

Inclusion

1. Any histologically and genetically confirmed Ewing sarcoma of bone or soft tissue, or round cell sarcomas which are 'Ewing's-like' but negative for EWSR1 gene rearrangement
2. Metastatic disease
3. Age ≥2 years and <50 years (from second birthday to 49 years 364 days)

4. Patient assessed as medically fit to receive the Ewing sarcoma standard multimodal treatment and regorafenib, including:

   • Absolute Neutrophil Count (ANC) ≥ 0.75x10^9/L, platelets ≥ 75x10^9/L.
   • Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 5×ULN
   • Bilirubin ≤ 2×ULN
   • Creatinine < 2x ULN or creatinine clearance >60 ml/min/1.73 m^2
   • International normalized ratio (INR)/ Partial thromboplastin time (PTT). INR and PTT ≤ 1.5 x ULN. INR & PTT ≤ 1.5xULN
5. Adequate cardiac function as evidenced by left ventricular ejection fraction (LVEF) ≥50%) at baseline, as determined by echocardiography
6. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as: a BP <95th percentile for sex, age, and height at screening (as per National Heart Lung and Blood Institute [NHLBI] guidelines) and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1. Patients >18 years old should have BP ≤ 150/90 mmHg.
7. No prior treatment for Ewing sarcoma other than surgery
8. Negative pregnancy test for female patients of childbearing potential within 7 days prior to study registration.
9. Patient agrees to use highly effective contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where applicable
10. Subject must be able to swallow and retain oral medication.
11. Written informed consent from the patient and/or the parent/legal guardian, according to local, regional or national regulation prior to any study specific procedures.
12. Patients must be affiliated to a social security system or beneficiary of the same, as per local regulatory requirements (France only)