Ewing Sarcoma Cancer
Conditions
Interventions
Study entry
INTER-EWING-1 includes a study entry point where all patients with Ewing sarcoma (ES) may give consent for the analysis of their biological samples and/or undergo additional scans, alongsi
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
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: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Randomisation A (Induction chemotherapy): OS, Toxicity, QoL, Histological response (if surgery is performed) Randomisation B1 (Radiotherapy): LFFS, OS, Toxicity, Achievement of local control, Acute post radiotherapy toxicity, Late toxicity, QoL Randomisation B2 (Radiotherapy): LFFS, OS, Toxicity, Achievement of local control, Acute post radiotherapy toxicity, Late toxicity, QoL Randomisation C (Maintenance therapy): OS, toxicity, QoL OS – Overall survival time measured using patient records QoL – Cancer quality of life measures (PedsQL and EORTC QLQ-C30) LFFS – Local failure-free survival time measured using patient records Adverse events and toxicity will be categorised and graded using CTCAE v5.0. Histological response is the percentage of viable tumour cells observed post-induction chemotherapy surgery of the primary tumour. Achievement of local control is radiologically confirmed at the end of treatment. Acute post radiotherapy toxicity is defined as a radiotherapy related adverse event grade 3 and above during and up to 120 days after completing radiotherapy Late toxicity is defined as radiotherapy related adverse event grade 3 and above occurring from 120 days after completing radiotherapy | — |
Countries
Australia, Denmark, England, France, Italy, Netherlands, New Zealand, Northern Ireland, Norway, Poland, Scotland, Spain, Switzerland, Wales
Outcome results
None listed