iEuroEwing

Author:  Julia Dobke, Last modification: 2023/09/27 https://kinderkrebsinfo.de/doi/e274127

iEuroEwing INTERNATIONAL EURO EWING TRIAL FOR TREATMENTOPTIMISATION IN PATIENTS WITH EWING SARCOMA
Disease Patients with localised standard-risk (SR) or metastatic high-risk (HR) primary diagnosed Ewing sarcoma or Ewing-like sarcoma over 2 and under 50 years of age
Type International phase III, open label, multi-centre, randomised, collaborative treatment optimizing trial.
Rationale / Objectives

Standard-arm (local disease)

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 localised disease.
iEuroEwing-SR RT-part:
The main goal is to show in a randomised setting, that a higher Radiotherapy dose is not inferior regarding an acute skin toxicity CTCAE grade ≥3 under radiotherapy. A further goal is to investigate, whether a higher dose of radiation improves event-free survival since randomisation 1.

Highrisk-arm (metastatic disease)

  • 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.
Therapy / Study arms

Standard SR arm A:
Chemotherapy: The standard SR arm A consists of nine cycles of alternating VDC and IE induction, before local control and five cycles of alternating IE and VC. For patients randomised in the standard SR arm A, treatment ends with the completion of consolidation therapy.
Radiotherapy: Je nach individueller Risikoeinschätzung werden die zu einer Randomisierung zugelassenen Patienten in vier Gruppen eingeteilt (Adjuvant low risk; Adjuvant high risk; Definitiv low risk; Definitiv high risk) und innerhalb dieser Gruppe in den Standard-Arm A (A1 45 Gy, A2 50.4 Gy,A3 54 Gy and A4 59.4 Gy) oder den Experimentellen Arm-B (B1 54 Gy, B2 59.4 Gy, B3 63 Gy and B4 68.4 Gy) randomisiert.
Standard SR Arm B:
Chemotherapy:Similar to the standard SR arm A, the experimental SR arm B consists of nine cycles of alternating VDC and IE induction, before local control and five cycles of alternating IE and VC. In contrast to the standard SR arm A, patients in the experimental SR arm B receive additional maintenance therapy with VinoCyc.
Radiotherapy: Patients will be treated as decribed in the iEuroEwing-SR part. Eligible patients will undergo a randomisation for the local radiotherapy between lower radiotherapy dose in the arms A1 45 Gy, A2 50.4 Gy, A3 54 Gy and A4 59.4 Gy and the higher radiotherapy dose in the arms B1 54 Gy, B2 59.4 Gy, B3 63 Gy and B4 68.4 Gy, to the primary tumour site and/or residual tumour.

Highrisk arm-A
Chemotherapy:The standard HR arm A consists of nine cycles of alternating VDC and IE induction, before local control and five cycles of alternating IE and VC. For patients randomised in the standard HR arm A, treatment ends with the completion of consolidation therapy.
Highrisk arm-B
Chemotherapy:Similar to the standard HR arm A, the experimental HR arm B consists of nine cycles of alternating VDC and IE induction, before local control and five cycles of alternating IE and VC. In contrast to the standard HR arm A, patients in the experimental HR arm B receive additional maintenance therapy with VinoCyc.

According to the results of the EURO-E.W.I.N.G 99 and Ewing 2008 R2loctrials, a subgroup of patients with poor histological response to induction chemotherapy may be referred to a high-dose treatment with busulfan and melphalan (BuMel), with an autologous stem cell transplantation.

Inclusion Criteria
  • 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
  • Any sex, age over 2 and under 50 years by the date of diagnostic biopsy (Patients outside this age range may be included in the iEuroEWING registry, contact: iEuroEwing@uk-essen.de)
  • 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.
  • White blood cell (WBC) count over 2000/μl*
  • Assessment of cardiac function including LVEF over 40 % and SF over 28 %*
  • Serum creatinine under 1.5 X ULN*
  • 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
Exclusion Criteria
  • Treatment of more than one cycle of chemotherapy prior to registration in the SR group
  • 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.
  • Clinically significant and uncontrolled, or active cardiac disease
  • Evidence of invasive fungal infection or other severe systemic infection requiring systemic / parenteral therapy
  • 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).
  • Secondary malignancy
  • Pregnancy or lactation
  • Female and male subjects with child-bearing potential, who avoid using highly effective contraceptive methods
  • Any other medical, psychiatric or social condition which is incompatible with the protocol treatment
  • Contraindications according to the respective applicable SmPCs
  • Patients who receive preoperative RTX
  • Patients who receive Brachytherapy
  • Patients who have been diagnosed with pleural effusion
  • Patients with previous RT in the same region
Recruitment SR-group: 730, HR-group: 288
Status Start 2023, Rekruitment planned for 6,5 years
EudraCT 2019-004153-93
Entry Study Register
Principal Investigator Prof. Dr. med. Uta Dirksen
E-Mail iEuroEwing@uk-essen.de
Contact

National Principal Investigator

Prof. Dr. med. Uta Dirksen Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin Kinderheilkunde III, Internationale EWING Studienzentrale Hufelandstr. 55 45147 Essen Telefon +49 (201) 723 8084 Fax +49 (201) 723 6298

Trail Coordiantion

Andreas Löcken Telefon +49 (0)201 723-8082 Fax +49 (0)201 723-6298

Tumorbaord

Diana Wieser Universitätsklinikum Essen (AöR) Zentrum für Kinder- und Jugendmedizin Klinik für Kinderheilkunde III; Internationale EWING Studienzentrale Hohlweg 8 45147 Essen Telefon +49 (0)201 723-8084 Fax +49 (0)201 723-6298 itb-ewing@uk-essen.de

Study-office

Diana Wieser Universitätsklinikum Essen (AöR) Zentrum für Kinder- und Jugendmedizin Klinik für Kinderheilkunde III; Internationale EWING Studienzentrale Hohlweg 8 45147 Essen Telefon +49 (0)201 723-8084 Fax +49 (0)201 723-6298

Participants AGPHO Arbeitsgruppe für Pädiatrische Hämatologie und Onkologie (Österreich) BSPHO Belgian Society of Paediatric Haematology Oncology Czech Czech Paediatric Oncology Cyprus Pediatric Oncology Cyprus EORTC European Organisation for Research and Treatment of Cancer Finland Helsinki University GPOH Gesellschaft für Pädiatrische Onkologie und Hämatologie Greece Hellenic Society of Pediatric Hematology-Oncology Israel Israel Society of Pediatric Hematology and Oncology Hungary Semmelweis University Budapest ISG Italian Sarcoma Group Lithuania Santariskiu Klinikos, Affiliate of Vilnius University Hospital Poland Polish Sarcoma Group Portugal Pediatric Oncology Portugal SSG Scandinavian Sarcoma Group (Sweden) Slovenia Slovenian Society of Paediatric Oncology SPOG Swiss Paediatric Oncology Group SAKK
Sponsoring Deutsche Krebshilfe