ViKTriY-PC Consortium Phase II Supplement

 描述(申请人提供)：药物开发的新时代代表着相对于不考虑潜在的肿瘤基因组学、生物学和免疫学的“传统”治疗方法而言，早期研究被视为是一种范式的转变。翻译终点，包括靶标表达水平、参与程度和下游效应器的调节，正在尽可能早地进行评估，并越来越重视早期患者选择，利用新的生物标记物分析和分子特征来识别最有可能反应的患者。随着这些终点变得越来越常见，传统的临床试验分类为不同的1期或2期研究往往是不够的。相反，这些研究已被混入“早期临床试验”分类，进行这些研究需要更广泛的专业知识。NCI实验治疗-临床试验网络(ET-CTN)的最终目的是定义更好的方法来开发新的抗癌药物，这些药物利用从分子上表征肿瘤的能力，并找到适当的生物标记物来选择最有可能对特定药物有反应的患者。虽然最初的ET-CTN UM1拨款侧重于第一阶段，但通过将第二阶段临床试验合并到网络中来扩大活动范围，可以更好地实现这一目标。本申请是对我们的母公司ETCTN UM1奖(1UM1CA186689)的修订，目的是描述我们进行第二阶段临床试验的能力。我们在最初的合作伙伴关系中增加了两个机构，并将其命名为Vanderbilt-Ingram，Karmanos，TGen研究所，耶鲁-太平洋海岸(加州大学圣地亚哥分校和加州大学旧金山分校)(ViKTriY-PC)。随着第二阶段能力的增加，我们团队的目标是：1)利用机构科学，利用CTEP产品组合开发针对罕见癌症、常见癌症和常见癌症的罕见变异的第二阶段试验；2)将血清、组织和成像生物标记物纳入新的第二阶段试验，以更好地了解新药物单独或联合使用的效果；3)培养在第一阶段和第二阶段进行早期临床试验的有知识和熟练的研究员和初级教员，并帮助他们将有希望的试验推进到第三阶段。这个团队的成员在协作研究和指导下一代癌症研究人员方面拥有一套独特的互补专业知识和相似的哲学。ViKTriY-PC团队致力于利用他们的专业领域，最大限度地利用他们的合作关系，在ET-CTN内进行尖端的1期和2期试验，最终使命是改善癌症患者的预后。

 DESCRIPTION (provided by applicant): The new era in drug development represents a paradigm shift in how early phase studies are considered relative to the "conventional" approach of treating without consideration to underlying tumor genomics, biology and immunology. Translational endpoints, including levels of target expression, engagement, and modulation of downstream effectors are being assessed as early as possible, and increasing emphasis is being placed on early patient selection, utilizing novel biomarker assays, and molecular characterization to identify patients most likely to respond. As these endpoints have become more common, the traditional classification of clinical trials as distinct Phase 1 or Phase 2 studies is often insufficient. Rather, these studies have become blended into an "early clinical trial" classification, and a wider range of expertise is necessary to conduct them. The ultimate purpose of the NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN) is to define better approaches for the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly and find appropriate biomarkers to select patients most likely to respond to specific agents. While the original ET-CTN UM1 grant had a Phase 1 emphasis, this goal can be better achieved by expanding the scope of activities by merging Phase 2 clinical trials into the Network. This application is a revision to our parent ETCTN UM1 award (1UM1CA186689) with the purpose of describing our capabilities to conduct Phase 2 clinical trials. We have added 2 institutions to our original partnership, and have termed it Vanderbilt-Ingram, Karmanos, TGen Research Institute, Yale - Pacific Coast (University of California-San Diego and University of California-San Francisco) (ViKTriY - PC). As Phase 2 capabilities are added, our team aims to 1) leverage institutional science to develop Phase 2 trials using the CTEP portfolio in rare cancers, common cancers, and uncommon variants of common cancers; 2) incorporate serum, tissue and imaging biomarkers into novel Phase 2 trials to better understand the effects of novel agents either alone or in combination; 3) and develop fellows and junior faculty who are knowledgeable and proficient in conducting early phase clinical trials across the Phase 1 and 2 spectrum, and help them advance promising trials to Phase 3. The members of this team have a unique set of complementary expertise and a similar philosophy regarding collaborative research and mentorship of the next generation of cancer investigators. This ViKTriY-PC team is committed to utilizing their areas of expertise and maximizing their collaborative relationships to conduct cutting- edge Phase 1 and 2 trials within the ET-CTN with the ultimate mission of improving outcomes for patients with cancer.