International clinical research programme to improve outcomes in newly diagnosed Ewing sarcoma – Trial 1 (INTER-EWING-1)

ACTRN 12624000532505

Brief Summary

Ewing Sarcoma is a cancer of bone or soft tissue that occurs in children and adults. Treatment usually includes chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells, surgery and/or radiotherapy. This is an international clinical trial (INTER-EWING-1) that will assess multiple combinations of these treatment types to determine whether different combinations are better able to improve survival for patients with Ewing Sarcoma.

Intervention/Treatment

• Drug: Regorafenib.

Inclusion Criteria

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-Fli gene rearrangement.
2. Age > 2 years.
3. Written informed consent from the patient and/or the parent/legal guardian

Inclusion criteria for randomisation A will be defined on completion of the externally sponsored phase 1b study (ClinicalTrials.gov Identifier: NCT05830084, EudraCT No: 2022-002874-10). A substantial amendment will be submitted to the relevant competent authority and ethics committee(s) to include these details prior to the opening of Randomisation A.

Radiotherapy Randomisations – B1 and B2
Inclusion Criteria

1. Entered into the INTER-EWING-1 study.
2. Received induction/consolidation chemotherapy with a VDC/IE/VC/VAI/BuMel based regimen.
3. Patient assessed as medically fit to receive the radiotherapy.
4. Documented negative pregnancy test for female patients of childbearing potential.
5. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active.
6. Written informed consent from the patient and/or the parent/legal guardian.

Randomisation B1 specific Inclusion criteria– Definitive radical radiotherapy dose finding randomisation

1. Patients requiring definitive radical radiotherapy to primary tumour site as sole local therapy following discussion by local multidisciplinary team.
2. Patients who have undergone an R2 resection of the primary tumour (macroscopic residual tumour), requiring definitive radical radiotherapy.

Randomisation B2 specific Inclusion criteria– Post-operative radiotherapy dose finding randomisation

1. Patients requiring post-operative radiotherapy following discussion by local multidisciplinary team
   according to multidisciplinary team meeting.

Randomisation C – Maintenance chemotherapy randomisation
Inclusion Criteria

1. Entered into the INTER-EWING-1 study.
2. Received induction/ consolidation chemotherapy with a VDC/IE/VC/VAI/BuMel based regimen.
3. Have responded to induction treatment and not progressed.
4. Medically fit to receive treatment.
5. Absence of severe vincristine neuropathy – i.e. requiring discontinuation of vincristine treatment.
6. Adequate liver function: bilirubin <3 x ULN and ALT or AST < 5 x ULN
7. Documented negative pregnancy test for female patients of childbearing potential.
8. Patient agrees to use contraception during therapy and for 12 months after last trial treatment (females) or 6 months after last trial treatment (males), where patient is sexually active.
9. Written informed consent from the patient and/or the parent/legal guardian.