BACKGROUND Although there have been multiple randomised trials in newly diagnosed Ewing sarcoma family of tumours (ESFT) and these have been conducted over many years and involved many international cooperative groups, the outcomes for all stages of disease have plateaued. Internationally, the standard treatment of ESFT is not defined, and there is a need to add new agents other than conventional chemotherapy to improve outcomes. This trial will compare two different induction/consolidation chemotherapy regimens: (1) vincristine, ifosfamide, doxorubicin and etoposide (VIDE) induction and vincristine, actinomycin D, ifosfamide or cyclophosphamide, or busulfan and mephalan (VAI/VAC/BuMel) consolidation and (2) vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) induction and ifosfamide and etoposide, vincristine and cyclophosphamide, vincristine, actinomycin D and ifosfamide, or busulfan and mephalan (IE/VC/VAI/BuMel) consolidation (randomisation 1, or R1). A second randomisation (R2) will determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome. METHODS EURO EWING 2012 is an international, multicentre, phase III, open-label randomised controlled trial. There are two randomisations: R1 and R2. Patients are randomly assigned at two different time points: at entry to the trial (R1) and following local control therapy (R2). The primary outcome measure is event-free survival. The secondary outcome measures include overall survival, adverse events and toxicity, histological response of the primary tumour, response of the primary tumour, regional lymph nodes or metastases (or both), and achievement of local control at the end of treatment. DISCUSSION This study will establish which is the "standard regimen" of chemotherapy, taking into account both clinical outcomes and toxicity. This will form the chemotherapy backbone for future interventional studies where we may want to add new targeted agents. It will also determine the role of zoledronic acid in conjunction with the separate EE2008 trial. Any trial in ESFT needs to take into account the rarity of the tumour and consider that international cooperation is needed to provide answers in a timely manner. TRIAL REGISTRATION Registered with EudraCT number 2012-002107-17 on 26 February 2012. Registered with ISRCTN number 54540667 on 4 November 2013.

中文翻译：

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用于治疗新诊断的 EWING 肉瘤家族肿瘤的国际随机对照试验 - EURO EWING 2012 方案。


背景尽管针对新诊断的尤文肉瘤家族肿瘤（ESFT）进行了多项随机试验，并且这些试验已经进行了多年并涉及许多国际合作团体，但疾病所有阶段的结果都已趋于稳定。国际上尚未明确ESFT的标准治疗方法，需要在常规化疗之外添加新的药物来改善预后。该试验将比较两种不同的诱导/巩固化疗方案：(1) 长春新碱、异环磷酰胺、阿霉素和依托泊苷 (VIDE) 诱导和长春新碱、放线菌素 D、异环磷酰胺或环磷酰胺，或白消安和美法仑 (VAI/VAC/BuMel) 巩固和 ( 2) 长春新碱、多柔比星、环磷酰胺、异环磷酰胺和依托泊苷 (VDC/IE) 诱导以及异环磷酰胺和依托泊苷、长春新碱和环磷酰胺、长春新碱、放线菌素 D 和异环磷酰胺，或白消安和美法仑 (IE/VC/VAI/BuMel) 巩固（随机化 1 ，或R1）。第二次随机分组 (R2) 将确定在巩固化疗中添加唑来膦酸（如 R1 所示）是否与改善临床结果相关。方法 EURO EWING 2012 是一项国际、多中心、III 期、开放标签随机对照试验。有两种随机化：R1 和 R2。患者在两个不同的时间点被随机分配：进入试验时（R1）和局部对照治疗后（R2）。主要结果指标是无事件生存率。次要结果指标包括总生存率、不良事件和毒性、原发肿瘤的组织学反应、原发肿瘤的反应、区域淋巴结或转移（或两者）以及治疗结束时局部控制的实现情况。 讨论 本研究将考虑临床结果和毒性，确定化疗的“标准方案”。这将成为未来介入研究的化疗支柱，我们可能希望在其中添加新的靶向药物。它还将结合单独的 EE2008 试验确定唑来膦酸的作用。 ESFT的任何试验都需要考虑到肿瘤的罕见性，并考虑需要国际合作来及时提供答案。试用注册 于 2012 年 2 月 26 日注册于 EudraCT，编号为 2012-002107-17。于 2013 年 11 月 4 日注册于 ISRCTN，编号为 54540667。