C40 C41
Conditions
Interventions
Group 1: SR Part*:
Arm A:
The standard SR arm A consists of nine cycles of alternating VDC and IE induction, before local control and five cycles of alternating VC and IE. For patients randomised in t
d 1
IV push or short infusion
DOXORUBICIN: 37.5 mg/m2/d
d 1, 2
IV infusion, 24 h
CYCLOPHOSPHAMIDE: 1200 mg/m2/d
IV infusion, 1 h
2-MERCAPTOETHANE: 500 mg/m2/d
IV push, 1 h prior to Cyclophosphamide
SULFONATE (MESNA): 1500 mg/m2/d
IV infusion, 24 h
IE:
IFOSFAMIDE: 1800 mg/m2/d
d 1-5
IV infusion, 4 h
2-MERCAPTOETHANE: 1.0 g/m2/d
IV push 1 h prior to Ifosfamide
SULFONATE (MESNA): 2.0 g/m2/d
IV infusion, 24 h
ETOPOSIDE: 100 mg/m2/d
d 1-5: IV infusion, 2 h
Group 2: SR Part*:
Arm B:
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
Sponsors
Gesellschaft für pädiatrische Onkologie und Hämatologie (GPOH)
Eligibility
Sex/Gender
All
Age
2 Years to 49 Years
Inclusion criteria
Inclusion criteria: Diagnosis: Primary diagnosed and histologically confirmed, localised (SR) or metastatic (HR) Ewing sarcoma or Ewing-like sarcoma of bone and/or soft tissue Age and sex: Any sex, age >2 and 2000/µl Cardiological parameters*: Left ventricular ejection fraction (LVEF) > 40%, shortening fraction (SF) > 28% Serum creatinine < 1.5 X ULN* *checked within 45 days from biopsy to the start of protocol treatment Contraception: 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 informed consent form (ICF) until 6 months after the end of treatment.
Exclusion criteria
Exclusion criteria: • Treatment of more than one cycle of chemotherapy prior to registration • 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 iEuroEwing-SR-RT part: • Primary diagnosed and histologically confirmed, localised (SR) Ewing sarcoma or Ewing-like sarcoma of bone and/or soft tissue and indication for radiotherapy except of whole lung irradiation. • Patients who receive preoperative RTX • Patients who receive Brachytherapy • Patients with previous RT in the same region
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Occurrence of acute skin toxicity CTCAE grade=3 under radiotherapy: 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 radiotherapy. The non-inferiority margin for the risk difference is 8% between the combined standard and combined experimental arms. - EFS: iEuroEwing-SR part: The main goal is to conduct a randomised trial arm. This will examine, whether the addition of a maintenance treatment using VinoCyc to nine cycles of VDC/IE improves EFS in patients with primary a localised disease, aiming at a 10% increase of a 3-year EFS since the end of consolidation therapy, compared to the standard VDC/IE treatment alone. iEuroEwing-HR part: The main goal is to conduct a randomised trial arm. 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 since the end of consolidation therapy, compared to the standard VDC/IE treatment alone. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Local control iEuroEwing-SR-RT part: : A further goal is to investigate, whether a higher dose of radiation improves local control since randomisation 1. A further goal is to investigate, whether a higher dose of radiation improves event-free survival since randomisation 1. A further goal is to investigate, whether a higher dose of radiation improves overall survival since randomisiation 1. iEuroEwing-SR part: A further goal is to investigate, whether the introduction of metronomic maintenance therapy adding VinoCyc in a randomised design compared to the standard VDC/IE treatment alone improves OS, aiming at a 10% increase, and whether the 3-year OS improves compared to historical controls. iEuroEwing-HR part: A further goal is to investigate, whether the introduction of metronomic maintenance therapy adding 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. - Toxicity / Safety: A further goal is to evaluate both short-term and long-term toxicity. - Survival outcome: A further goal is to analyse outcome (EFS, OS) in the entire group of randomised and non-randomised patients. Further Secondary Objectives: Further goals are to assess the following features among patients: - Quality of life - Time to diagnosis - Cancer predisposition - Correlation of histopathological response with imaging data - Biology of Ewing sarcoma | — |
Countries
Austria, Belgium, Czechia, Finland, France, Germany, Greece, Hungary, Israel, Lithuania, Netherlands, Poland, Slovakia, Slovenia, Sweden
Contacts
Public ContactUta Dirksen
Universitätslinikum Essen
Outcome results
None listed