INTER-EWING-1: International Clinical Research Programme to Improve Outcomes in Newly Diagnosed Ewing Sarcoma – Trial 1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The University Of Birmingham

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Sep 2025 → ongoing

Decision date (initial)

2025-07-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Cancer Research UK · INCA (institute National du cancer) · Juegaterapia · Danish Childhood Cancer Foundation · National Advisory Unit sarcoma · Fundación Aless Lequio · LIGUE contre le cancer

External identifiers

EU CT number

2024-511989-36-00

ISRCTN

ISRCTN17938906

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objectives for this trial are related to each of the trial questions.

For the chemotherapy questions, the objectives are to determine:
• Whether outcome in newly diagnosed metastatic ES patients can be improved with the addition of regorafenib to the standard backbone chemotherapy VDC/IE when compared with VDC/IE alone (Randomisation A)
• Whether the addition of 6 cycles of maintenance chemotherapy of vinorelbine and cyclophosphamide improves the outcome for patients. (Randomisation C)

For the radiotherapy questions, the objectives are to determine:
• Whether dose escalation of radiotherapy improves the outcome in patients with inoperable disease (Randomisation B1)
• Which of the two post-operative radiotherapy doses following surgical resection of the primary tumour site will result in achieving optimal outcome (Randomisation B2)

Secondary objectives 3

1. Randomisation A: Induction chemotherapy Overall Survival, Toxicity, Cancer Quality of Life Measures, Histological response (if surgery is performed)
2. Randomisations B1 & B2: Radiotherapy Local Failure-Free Survival Time, Overall Survival, Toxicity, Achievement of local control, Acute post-radiotherapy toxicity, Late toxicity, Cancer Quality of Life Measures
3. Randomisation C: Maintenance therapy Overall Survival, Toxicity, Cancer Quality of Life Measures

Conditions and MedDRA coding

Ewing Sarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. Study Entry: 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. Randomisation B1: 1. Patients requiring definitive radical radiotherapy to primary tumour site as sole local therapy following discussion by local multidisciplinary team (see INTER-EWING-1 QUARTET RTQA guidelines on factors to be considered for definitive radiotherapy). This includes patients who have undergone an R2 resection of the primary tumour (macroscopic residual tumour), requiring definitive radical radiotherapy
3. Randomisation B2: 1. Patients requiring post-operative radiotherapy following discussion by local multidisciplinary team at the multidisciplinary team meeting
4. Study Entry: 2. Age ≥ 2 years
5. Study entry: 3. Written informed consent from the patient and/or the parent/legal guardian
6. Randomisation B1 & B2: 1. Entered into the INTER-EWING-1 study
7. Randomisation B1 & B2: 2. Received induction/consolidation chemotherapy with a VDC/IE/VC/VAI/BuMel based regimen
8. Randomisation B1 & B2: 3. Patient assessed as medically fit to receive the radiotherapy
9. Randomisation B1 & B2: 4. Documented negative pregnancy test for female patients of childbearing potential
10. Randomisation B1 & B2: 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
11. Randomisation B1 & B2: 6. Written informed consent from the patient and/or the parent/legal guardian
12. Randomisation A: To be further defined on completion of the externally sponsored phase 1b study. substantial modification will be submitted to the relevant competent authority and ethics committee(s) to include these details prior to the opening of Randomisation A.
13. Randomisation C: 1. Entered into the INTER-EWING-1 study
14. Randomisation C: 2. Received induction/ consolidation chemotherapy with a VDC/IE/VC/VAI/BuMel based regimen
15. Randomisation C: 3. Have responded to induction treatment and not progressed
16. Randomisation C: 4. Medically fit to receive treatment
17. Randomisation C: 5. Absence of severe vincristine neuropathy – i.e. requiring discontinuation of vincristine treatment
18. Randomisation C: 6. Adequate liver function: bilirubin <3 x ULN and ALT or AST < 5 x ULN
19. Randomisation C: 7. Documented negative pregnancy test for female patients of childbearing potential
20. Randomisation C: 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 (see section 5)
21. Randomisation C: 9. Written informed consent from the patient and/or the parent/legal guardian

Exclusion criteria 14

1. Study entry: 1. Previous malignancy
2. Randomisation B1 & B2: 1. Previous radiotherapy to the same site
3. Randomisation B1 & B2: 2. Pregnant or breastfeeding women
4. Randomisation B1 & B2: 3. BuMel high dose chemotherapy within previous 10 weeks
5. Randomisation B1: 1. Patients who have had a R1 or R0 surgical resection of their tumour
6. Randomisation B1: 2. Previous high dose chemotherapy including busulfan when specified dose constraints to critical organs cannot be met
7. Randomisation B2: 1. R2 resection (macroscopic residual tumour)
8. Randomisation B2: 2. Patients treated by surgery with wide resection (R0 and all tissues involved by the prechemotherapy tumour volume have been completely resected) and have good histological response (< 10% viable cells), small tumour volume (< 200 mls at diagnosis), of the limb.
9. Randomisation A: To be further defined on completion of the externally sponsored phase 1b study. substantial modification will be submitted to the relevant competent authority and ethics committee(s) to include these details prior to the opening of Randomisation A.
10. Randomisation C: 1. Urinary outflow obstruction that cannot be relieved prior to starting treatment
11. Randomisation C: 2. Uncontrolled significant inter-current illness or active infection
12. Randomisation C: 3. Active inflammation of the urinary bladder (cystitis)
13. Randomisation C: 4. Known contraindication or hypersensitivity to any of the treatments or excipients
14. Randomisation C: 5. Pregnant or breastfeeding women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary end point for all randomisations is Event-free survival, defined as the time from randomisation until first failure event

Secondary endpoints 3

1. Randomisation A: Induction chemotherapy Overall Survival, Toxicity, Cancer Quality of Life Measures, Histological response (if surgery is performed)
2. Randomisations B1 & B2: Radiotherapy Local Failure-Free Survival Time, Overall Survival, Toxicity, Achievement of local control, Acute post-radiotherapy toxicity, Late toxicity, Cancer Quality of Life Measures
3. Randomisation C: Maintenance therapy Overall Survival, Toxicity, Cancer Quality of Life Measures

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The University Of Birmingham

Sponsor organisation

The University Of Birmingham

Address

Vincent Drive

City

Birmingham

Postcode

B15 2TT

Country

United Kingdom

Scientific contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Public contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Third parties 8

Locations

5 EU/EEA countries · 63 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications