Clinical Trials and Translation

摘要/摘要 高危神经母细胞瘤(NB)仍然是一个治疗挑战，预计5年总存活率不会超过 超过50%，尽管在过去20年中清髓治疗取得了进展，区分治疗和 免疫学和基因靶向治疗。核心B是我们多学科的翻译关键 和多机构P01，神经母细胞瘤(NB)治疗的发现和开发机制 抵抗。核心B的目标将通过成熟的神经母细胞瘤新方法来实现 治疗(NANT)联盟，总体目标是利用我们的临床试验专业知识和 基础设施，以支持新疗法的翻译，并展示临床前活动 在项目1-5中开发的复发和难治性(耐药)NB应用于临床护理，以最终改善 患有高危NB的儿童存活率较低。这个核心的三个具体目标是：1)提供 临床专业知识，用于翻译项目1-5与统计核心和 项目调查员；2)为快速实施提供已建立和可适应的基础设施 进入早期临床试验；3)为嵌入式相关研究提供基础设施，并提供独特的 高度注释的肿瘤组织、骨髓、血液和放射图像的生物信息库 耐药的NB患者，进行基因组和病理分析。核心B将获得安全性、机械性和 来自1/2阶段试验的反应数据，以支持将在更大范围内测试的项目1-5中的有希望的疗法 国家和国际第二阶段和第三阶段试验。这款高度集成的P01将允许从 实验室对患者进行个体化治疗，利用更精确的生物标志物进行反应。因此， 核心B将对该计划的总体成功作出实质性贡献，并最终改善高风险的NB 病人结局。

SUMMARY/ABSTRACT High-risk neuroblastoma (NB) remains a therapeutic challenge with expected 5-year overall survival of no more than 50%, despite advances in the past two decades with myeloablative therapy, differentiating therapy and immunologic and genetically targeted therapies. Core B is the translational linchpin of our multi-disciplinary and multi-institutional P01, Discovering and Exploiting Mechanisms of Neuroblastoma (NB) Therapy Resistance. The goal of Core B will be enabled by the well-established New Approaches to Neuroblastoma Therapy (NANT) consortium, and has the overall objective of capitalizing on our clinical trials expertise and infrastructure to support the translation of new therapies with demonstrated pre-clinical activity against relapsed and refractory (resistant) NB developed in Projects 1-5 into clinical care, in order to ultimately improve the poor survival of children with high-risk NB. The three specific aims of this Core are: 1) to provide the clinical expertise for translation of preclinical work from Projects 1-5 collaboration with the statistical Core and the Project investigators; 2) to provide the established and adaptable infrastructure for rapid implementation into early phase clinical trials; 3) provide the infrastructure for embedded correlative studies, and a unique biorepository of highly annotated tumor tissues, bone marrow, blood, and radiologic images obtained from resistant NB patients, with genomic and pathologic analysis. Core B will obtain safety, mechanistic, and response data from phase 1/2 trials to support promising therapies from Projects 1-5 to be tested in larger national and international Phase 2 and 3 trials. This highly integrated P01 will allow rapid translation from laboratory to patients, with individualized treatment, utilizing more precise biomarkers of response. Thus, Core B will contribute substantively to the overall success of the Program and ultimately improved high-risk NB patient outcome.