International Euro Ewing (iEuroEwing) trial for treatment optimisation in patients with Ewing sarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GPOH gGmbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jun 2022 → ongoing

Decision date (initial)

2023-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

German Cancer Aid

External identifiers

EU CT number

2022-501180-40-00

EudraCT number

2019-004153-93

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis

Event-free survival (EFS):
iEuroEwing-SR part: The main goal is to conduct a randomised trial part. This will examine, whether the addition of a maintenance treatment using VinoCyc to nine cycles of VDC/IE improves EFS in patients with primary disease, aiming at a 10% increase of a 3-year EFS compared to the standard VDC/IE treatment.

iEuroEwing-SR part RT: The main goal is to show in a randomised setting, that a higher RT dose is not inferior regarding an acute skin toxicity CTCAE grade≥3 under RT. The non-inferiority margin for the risk difference is 8% between the combined lower dose and combined higher dose RT arms

iEuroEwing-HR part: The main goal is to conduct a randomised trial part. This will examine, whether the addition of a maintenance treatment using VinoCyc to nine cycles of VDC/IE improves EFS in patients with primary disseminated disease, aiming at a 17% increase of 2-year EFS compared to the standard VDC/IE treatment.

Secondary objectives 10

1. iEuroEwing-SR part: Investigation if the maintenance therapy with VinoCyc in a randomised design compared to the standard VDC/IE treatment alone improves overall survival (OS) since randomisation 2, aiming at a 10% increase, and whether the 3-year OS improves compared to historical controls.
2. iEuroEwing-SR-RT part: Investigation if a higher dose of radiation improves local control since randomisation 1 and if a higher dose of radiation improves EFS and OS since randomisation 1.
3. iEuroEwing-HR part: Investigation if the maintenance therapy with VinoCyc in a randomised design compared to the standard VDC/IE treatment alone improves OS, aiming at a 15% increase, and whether the 3-year OS improves compared to historical controls.
4. Toxicity / Safety
5. Survival outcome
6. Quality of life
7. Time to diagnosis
8. Cancer predisposition
9. Correlation of histopathological response with imaging data
10. Biology of Ewing sarcoma

Conditions and MedDRA coding

Ewing Sarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histologically (and molecularly) diagnosed primary localised (SR) or metastatic (HR) Ewing sarcoma or so called Ewing-like sarcoma ( i.e. translocation-positive small blue round cell sarcoma other than Rhabdomyosarcoma) of bone and / or soft tissue; pathological diagnosis can be performed at the investigational site
2. Any sex, age >2 and < 50 years by the date of diagnostic biopsy
3. Informed consent must be obtained according to national and GCP guidelines and signed prior to trial entry. Subjects and when applicable parental or legal representative(s) must understand and voluntarily provide permission to the ICF, prior to conducting any trial-related assessments / procedures. Willingness and ability to comply with scheduled visits and trial procedures are required.
4. White blood cell (WBC) count > 2000/μl*
5. Assessment of cardiac function including LVEF > 40% and SF > 28%*
6. Serum creatinine < 1.5 X ULN*
7. For patients of childbearing potential, a negative pregnancy test must be documented prior to enrolment and repeated every month during therapy. Female and male patients, who are fertile and sexually active, must agree to use an effective form of contraception from the time of signing the ICF until 6 months after the end of treatment. *Parameters must be checked within the screening phase of 45 days from biopsy biopsy / surgery and after diagnosis of metastatic disease to registration.

Exclusion criteria 15

1. Treatment of more than one cycle of chemotherapy prior to registration in the SR group
2. Concurrent treatment within any other clinical trials, excluding trials with different endpoints, which, due to the nature of their endpoints, must run parallel to iEuroEwing trial, e.g. studies on antiemetics, antimycotics, antibiotics, strategies for psychosocial support, etc.
3. Clinically significant and uncontrolled, or active cardiac disease
4. Evidence of invasive fungal infection or other severe systemic infection requiring systemic / parenteral therapy
5. Hypersensitivity to the active substance or other excipients contained in the investigational medical products listed in the summary of product characteristics (SmPC) or investigators brochure (IB).
6. Secondary malignancy
7. Pregnancy or lactation
8. Female and male subjects with child-bearing potential, who avoid using highly effective contraceptive methods
9. Any other medical, psychiatric, or social condition which is incompatible with the protocol treatment
10. Contraindications according to the respective applicable SmPCs
11. Additional exclusion criteria iEuroEwing-SR-RT part: Primary diagnosed and histologically confirmed metastatic (HR)
12. Additional exclusion criteria iEuroEwing-SR-RT part: Patients who receive preoperative RTX
13. Additional exclusion criteria iEuroEwing-SR-RT part: Patients who receive Brachytherapy
14. Additional exclusion criteria iEuroEwing-SR-RT part: Patients who have been diagnosed with pleural effusion
15. Additional exclusion criteria iEuroEwing-SR-RT part: Patients with previous RT in the same region

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. iEuroEwing-SR: Analysis of EFS
2. iEuroEwing-SR-RT: Analysis of the occurrence of acute skin toxicity CTCAE grade ≥3 during radiotherapy
3. iEuroEwing-HR: Analysis of EFS

Secondary endpoints 10

1. iEuroEwing-SR part: Investigation if the maintenance therapy with VinoCyc in a randomised design compared to the standard VDC/IE treatment alone improves overall survival (OS) since randomisation 2, aiming at a 10% increase, and whether the 3-year OS improves compared to historical controls.
2. iEuroEwing-SR-RT part: Investigation if a higher dose of radiation improves local control since randomisation 1 and if a higher dose of radiation improves EFS and OS since randomisation 1.
3. iEuroEwing-HR part: Investigation if the maintenance therapy with VinoCyc in a randomised design compared to the standard VDC/IE treatment alone improves OS, aiming at a 15% increase, and whether the 3-year OS improves compared to historical controls.
4. Toxicity / Safety
5. Survival outcome
6. Quality of life
7. Time to diagnosis
8. Cancer predisposition
9. Correlation of histopathological
10. Biology of Ewing sarcoma

Investigational products

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

Test 8

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GPOH gGmbH

Sponsor organisation

GPOH gGmbH

Address

Holsterhauser Platz 2, Holsterhausen Holsterhausen

City

Essen

Postcode

45147

Country

Germany

Scientific contact point

Organisation

Gpoh Gemeinnützige GmbH

Contact name

Prof. Dr. med. Uta Dirksen

Public contact point

Organisation

Gpoh Gemeinnützige GmbH

Contact name

Prof. Dr. med. Dirk Reinhardt

Third parties 3

Locations

8 EU/EEA countries · 117 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 253 files

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

Application history

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