International clinical research programme to improve outcomes in newly diagnosed Ewing sarcoma – Trial 1

Phase 3

• Conditions: Ewing Sarcoma; Cancer

• Registration Number: ISRCTN17938906
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-09-07
• Last Update Posted: 18 September 2023
• Study Completion: 2032-11-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

Inclusion Criteria for study entry – Mandatory first point of study entry, for all patients
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. 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 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 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

Exclusion Criteria

Exclusion Criteria for study entry
1. Previous malignancy

Exclusion criteria for randomisation A will be defined on completion of the externally sponsored phase 1b study. 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.

Exclusion Criteria Radiotherapy Randomisations – B1 and B2
1. Previous radiotherapy to the same site
2. Pregnant or breastfeeding women
3. BuMel high dose chemotherapy within previous 10 weeks

Randomisation B1 specific Exclusion criteria– Definitive radical radiotherapy dose finding randomisation
1. Patients who have had a R1 or R0 surgical resection of their tumour
2. Previous high dose chemotherapy including busulfan when specified dose constraints to critical organs cannot be met (please see INTER-EWING-1 Quartet RTQA guidelines for more details)

Randomisation B2 specific Exclusion criteria– Post-operative radiotherapy dose finding randomisation
1. R2 resection (macroscopic residual tumour)
2. Patients treated by surgery with wide resection (R0 and all tissues involved by the prechemotherapy
tumour volume have been completely resected), good histological response (< 10% viable cells), small tumour volume (< 200 mls at diagnosis), of the limb.

Randomisation C – Maintenance chemotherapy randomisation
Exclusion Criteria
1. Urinary outflow obstruction that cannot be relieved prior to starting treatment
2. Uncontrolled significant inter-current illness or active infection
3. Active inflammation of the urinary bladder (cystitis)
4. Known contraindication or hypersensitivity to any of the treatments or excipients
5. Pregnant or breastfeeding women

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Event-free survival time (EFS), defined as the time from the date of each randomisation to the date of the first failure event, where failure events are defined as:1.1. Relapse or progression of existing disease, or recurrence of disease at new sites,1.2. Death from any cause without disease progression,1.3. Second malignant neoplasm.Patients without an event at the time of analysis will be censored at the date when they were last known to be alive and event-free.