Phase 3, Open Label, Multi-centre, Randomised Controlled International Study in Ewing Sarcoma
Ewing Sarcoma Primary objectives: Standard Risk R1: in a randomised trial, to examine whether add-on treatment with zoledronic acid in addition to induction and maintenance chemotherapy improves event-free survival in patients with localised Ewing sarcoma and good histological response or with initial tumour volume \<200 mL compared to no add-on treatment. \*High Risk R2: in a randomised trial, to examine whether high-dose chemotherapy using busulfan-melphalan with autologous stem cell reinfusion, compared with standard chemotherapy, improves event-free survival in patients with localised Ewing sarcoma and poor histological response or tumour volume ≥200 mL (R2loc). In patients with pulmonary metastases high dose busulfan-melphalan chemotherapy with autologous stem cell reinfusion is randomised versus standard chemotherapy plus whole lung irradiation (R2pulm). Very High Risk R3: in a randomised trial, to examine whether the addition of high dose chemotherapy using treosulfan-melphalan followed by autologous stem cell reinfusion to eight cycles of standard adjuvant chemotherapy, compared to eight cycles of standard adjuvant chemotherapy alone, improves event-free survival in patients with primary disseminated disease. \*R2 accrual discontinued on December 1st 2015.
• Diagnosis: Histologically confirmed Ewing sarcoma of bone or soft tissue.
• Age and sex: Either sex, age \>48 months (for GPOH patients) and \<50 years at the date of diagnostic biopsy. Younger or elderly patients may be reported to the appropriate office (see section 1.4) but are not included in this study.
• Registration: ≤ 45 days after diagnostic biopsy/surgery.
• Start of chemotherapy: ≤ 45 days after diagnostic biopsy/surgery.
• Informed consent: Must be signed prior to study entry.
• Performance status: Lansky or Karnofsky score \> 50%, may be modified for handicapped patients.
• Haematological parameters:
‣ Haemoglobin \> 8 g/dl (transfusion allowed),
⁃ Platelets \> 80.000/µl (transfusion allowed),
⁃ WBC \> 2000/µl.
• Cardiac values: LVEF \> 40%, SF \> 28%.