Phase 2 Clinical Trials Program for Experimental Therapeutics Clinical Trials Network

 描述（由申请人提供）：该拟议的UM 1 2期补充方案汇集了来自马约诊所、马里兰州大学、哥伦比亚大学和爱荷华州大学的NCI指定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，ETCTN团队的成员已经累计了3939名患者参加2期临床试验，展示了转化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志物，包括马约临床病理学研究中心和CLIA认证的马里兰州大学转化基因组实验室。我们现在建议对NCI申办的抗癌药物进行2期临床试验，以评估这些药物对其分子靶点的临床活性和生物学影响，阐明其他相关生物学效应，并确定临床结局与相关生物标志物和/或成像终点之间的相关性。这些研究的目的不仅是在与患者安全性相容的情况下有效地确定NCI选择的新抗癌药物或有前途的联合治疗和对药物开发至关重要的高优先级药物的有效性，而且还促进理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1期无缝地转移到2期，并提出可纳入其他机制赞助的3期临床试验的治疗方法。将使用适合于研究中特定药物治疗机制的临床终点设计研究，例如缓解、至进展时间、某个时间点的无进展率或生存期。重要的是，根据本补充资料进行的研究的替代或次要终点可能包括生物标志物终点或成像终点的变化，包括血流变化和/或肿瘤代谢活性的改变。因此，本提案的具体目的是：i）确定NCI选择的用于评价一系列恶性肿瘤治疗活性的新型抗癌剂和组合的临床活性、功效和安全性，无论是通过组织学亚型还是分子谱选择; ii）有效且无缝地将有希望的疗法从1期试验纳入2期试验; iii）评估翻译终点，例如与给定药剂或由所研究的药剂调节的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）鉴定和测试潜在的生物标志物（在可能的情况下，特别强调基因组学和成像），可作为疗效或毒性的预测因子;以及v）将来自R 01、SPORE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，这些临床试验使用团队科学方法来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.