Phase 2 Clinical Trials Program for Experimental Therapeutics Clinical Trials Network

 描述(由申请人提供)：这项拟议的UM1第二阶段补充材料汇集了来自NCI指定的梅奥诊所、马里兰大学、哥伦比亚大学和爱荷华大学的综合癌症中心的团队，共同进行早期临床试验。从2010年到2014年，这个拟议的ETCTN团队的成员已经积累了3939名患者参加第二阶段临床试验，展示了翻译科学方面的专业知识，并建立了专门的设施来开发临床试验的生物标记物，包括梅奥临床病理学研究核心和获得CLIA认证的马里兰大学翻译基因组实验室。我们现在建议进行NCI赞助的抗癌药物的第二阶段临床试验，以评估这些药物的临床活性和对其分子靶点的生物影响，阐明其他相关的生物效应，并确定临床结果与相关生物标志物和/或成像终点之间的相关性。这些研究的目标不仅是确定NCI选择的新抗癌药物或对药物开发至关重要的有希望的组合疗法和高优先级药物的有效性，而且还促进了解和适当开发这些药物所需的相关科学。其目的是将研究从第一阶段无缝转移到第二阶段，并提出可以纳入由其他机制赞助的第三阶段临床试验的治疗方法。研究将使用与研究中特定药物的治疗机制相适应的临床终点来设计，如反应、进展时间、某个时间点的无进展率或存活率。重要的是，根据本附录进行的研究的替代或次要终点可能包括生物标记物终点或成像终点的变化，包括血流的变化和/或肿瘤代谢活动的变化。因此，这项建议的具体目标是：i)确定NCI为评估一系列恶性肿瘤的治疗活性而选择的新型抗癌药物和组合的临床活性、有效性和安全性；ii)有效和无缝地将有希望的治疗从第一阶段进入第二阶段试验；iii)评估翻译终点，例如与研究中的药物调节的特定药物或途径相关的分子靶标和/或下游效应物的表达和/或活性水平；iv)识别和测试可能作为疗效或毒性预测因素的潜在生物标记物(特别强调基因组学和成像)；以及v)将来自R01、孢子或其他同行评审机制的临床前科学和新发现转化为临床试验，利用团队科学方法利用科学界的专业知识。

 DESCRIPTION (provided by applicant): This proposed UM1 phase 2 supplement brings together teams from NCI-designated comprehensive cancer centers at Mayo Clinic, University of Maryland, Columbia University, and the University of Iowa to collectively perform early phase clinical trials. Members of this proposed ETCTN team have accrued 3939 patients to phase 2 clinical trials from 2010 through 2014, demonstrated expertise in translational science, and established specialized facilities to develop biomarkers for clinical trials, including the Mayo Clinic Pathology Research Core and CLIA-certified University of Maryland Translational Genomic Laboratory. We now propose to conduct phase 2 clinical trials of NCI-sponsored anti-cancer agents to evaluate the clinical activity and biological impact of these agents on their molecular targets, elucidate other relevant biologic effects, and determine the correlation between clinical outcomes and relevant biomarkers and/or imaging endpoints. The goal of these studies is to not only determine, as efficiently as is compatible with patient safety, the effectiveness of new anticancer agents selected by the NCI or promising combination therapies and high- priority agents that are pivotal for drug development, but also facilitate the correlativ science needed to understand and properly develop these agents. The intent is to seamlessly move studies from phase 1 into phase 2 and to bring forward therapeutic approaches that can be incorporated into phase 3 clinical trials sponsored by other mechanisms. Studies will be designed using clinical endpoints that are appropriate for the therapeutic mechanism of the specific agent under study such as response, time to progression, progression- free rate at a point in time or survival. Importantly, alternative or secondary endpoints for the studies to be performed under this supplement may include changes in biomarker endpoints or imaging endpoints, including changes in blood flow and/or alterations in tumor metabolic activity. Accordingly, the specific aims of this proposal are to: i) determine the clinical activity, efficac and safety of novel anticancer agents and combinations selected by NCI for evaluation of therapeutic activity across a range of malignancies, whether chosen by histological subtype or molecular profile; ii) efficiently and seamlessly take promising therapies from phase 1 into phase 2 trials; iii) evaluate translational endpoints such as levels of expression and/or activity of molecular targets and/or downstream effectors pertinent to a given agent or pathway modulated by the agent under study; iv) identify and test potential biomarkers (with particular emphasis where possible on genomics and imaging) that may serve as predictors of efficacy or toxicity; and v) translate preclinical science and new discoveries from R01, SPORE or other peer reviewed mechanisms into clinical trials that leverage the expertise of the scientific community using a team science approach.