Southwest Early Clinical Trials Consortium

描述（由申请人提供）：科学和生物技术的最新进展导致了大量快速发展的高通量分析数据的爆炸式增长。虽然这些进展导致了一些难治性恶性肿瘤治疗的重大改进，但大多数晚期癌症仍然无法治愈。西南早期临床试验（SECT）联盟由德克萨斯大学MD安德森癌症中心和科罗拉多大学综合癌症中心组成，在战略和地理位置上处于领导、合作和执行NCI实验治疗-临床试验网络的I期临床试验的位置，在广泛的患者群体中，包括在几个服务不足的地区。具体而言，我们建议：1。以有效和协作的方式研究新药或假设驱动的新组合的安全性和临床活性。2. 分子分析患者（宿主组织）及其恶性肿瘤，以根据已确定的分子畸变，在适当的情况下，优化每位患者潜在相关治疗的选择。3. 开发临床相关的药效学反应标志物。4. 在ET-CTN和其他临床试验的领导、实施、分析和报告方面，酌情指导初级教员、实习生和研究人员。5. 在ET-CTN内提供科学和行政领导，包括积极参与项目团队，研究设计和协议开发，撰写/共同撰写网络组出版物，参与科学，行政或特设委员会，以及参加NCI中央irb和参加ET-CTN和IDSC会议。除了在临床试验累积、药代动力学和药效学评估方面建立的熟练程度外，SECT机构还拥有无与伦比的资源组合，包括获得广泛基因分型肿瘤的大量患者群体、建立的生物储存库、最先进的临床基因组学能力和专家生物信息学。在三位经验丰富、技能互补的主要研究人员的领导下，SECT联盟准备执行一种新的早期实验性治疗性临床试验范式，其目标是验证正确的途径，用正确的药物靶向三种途径，并在正确的患者中测试这些药物。

DESCRIPTION (provided by applicant): Recent advances in science and biotechnology have led to an explosion of data from the plethora of rapidly developing high throughput analyses. While these advances have led to major improvements in the therapy of several refractory malignancies, most advanced cancers remain incurable. The Southwest Early Clinical Trials (SECT) Consortium consists of University of Texas MD Anderson Cancer Center and University of Colorado Comprehensive Cancer Center, and is strategically and geographically placed to lead, collaborate on and execute phase I clinical trials in the NCI Experimental Therapeutics-Clinical Trials Network in broad patient populations, including in several underserved regions. Specifically, we propose to: 1. Study, in an efficient and collaborative manner, the safety and clinical activity of new agents or hypothesis-driven novel combinations. 2. Molecularly profile patients (host tissues) and their malignancies to optimize selection of potentially relevant therapy for each patient, based on identified molecular aberrations, where appropriate. 3. Develop clinically relevant pharmacodynamic markers of response. 4. Mentor junior faculty, trainees, and research personnel, as applicable, in the leadership, conduct, analysis, and reporting of ET-CTN and other clinical trials. 5. Provide scientific and administrative leadership within ET-CTN, including active participation in project teams, research design and protocol development, authorship/co-authorship of Network group publications, and participation in scientific, administrative, or ad hoc committees, as well as participation in the NCI Central IRBs and attendance at ET-CTN and IDSC meetings. In addition to established proficiency in clinical trial accrual, pharmacokinetics, and pharmacodynamic assessment, the SECT Institutions have an unparalleled combination of resources that include access to large patient populations with extensively genotyped tumors, established biorepositories, state of the art clinical genomics capabilities, and expert bioinformatics. Led by three experienced principle investigators with complementary skills, the SECT consortium is poised to execute a new paradigm for early experimental therapeutic clinical trials, with the goals to validate the right pathways, target thee pathways with the right drugs, and test these drugs in the right patients. RELEVANCE: Early oncology clinical trials have traditionally focused on defining the maximum tolerated dose for phase II development. Recent development of novel targeted agents demand a different approach that includes: 1) testing in a molecularly profiled population; 2) evaluation f intermediate biologic endpoints; and 3) determination of the optimal biologic dose for Phase II studies.