Clinical Trials and Translation

总结/摘要 高危神经母细胞瘤（NB）仍然是一个治疗挑战，预计5年总生存率不超过 超过50%，尽管在过去的二十年中，清髓性治疗，分化治疗和 免疫和基因靶向治疗。核心B是我们多学科的翻译关键 和多机构P01，发现和利用神经母细胞瘤（NB）治疗的机制 阻力核心B的目标将通过成熟的神经母细胞瘤新方法实现 治疗（NANT）财团，并有利用我们的临床试验专业知识和 基础设施，以支持新疗法的转化，并证明其临床前活性， 项目1-5中开发的复发性和难治性（耐药）NB进入临床护理，以最终改善 高危NB患儿生存率低。该核心的三个具体目标是：1）提供 与统计核心合作的项目1-5的临床前工作翻译的临床专业知识， 项目调查员; 2）提供快速实施所需的已建立和可调整的基础设施 进入早期临床试验; 3）为嵌入式相关研究提供基础设施， 高度注释的肿瘤组织、骨髓、血液和放射学图像的生物储存库， 耐药NB患者的基因组和病理分析。核心B将获得安全、机械和 来自1/2期试验的反应数据，以支持项目1-5中有前途的疗法， 国家和国际2期和3期试验。这种高度集成的P01将允许从 实验室对患者进行个体化治疗，利用更精确的反应生物标志物。因此，在本发明中， 核心B将为项目的整体成功做出实质性贡献，并最终改善高风险NB 患者结局。

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.