Southwest Early Clinical Trials Consortium

描述(申请人提供)：科学和生物技术的最新进展导致了来自快速发展的高通量分析的过多数据的爆炸性增长。虽然这些进展导致了几种难治性恶性肿瘤的治疗方面的重大改进，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先地位，可以在NCI实验治疗-临床试验网络中领导、合作和执行NCI实验治疗-临床试验网络的I期临床试验，包括在几个服务不足的地区。具体地说，我们建议：1.以高效和协作的方式研究新药物或假说驱动的新组合的安全性和临床活性。2.对患者(宿主组织)及其恶性肿瘤进行分子特征分析，以便在适当的情况下，基于已识别的分子异常，为每个患者优化潜在相关治疗的选择。3.开发临床相关的药效学反应标记物。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、受训人员和研究人员。5.在ET-CTN内提供科学和行政领导，包括积极参与项目小组、研究设计和方案制定、网络团体出版物的作者/合著者、参加科学、行政或特设委员会，以及参加NCI中央IRBs和参加ET-CTN和IDSC会议。除了在临床试验收益、药代动力学和药效学评估方面的成熟水平外，Sector机构还拥有无与伦比的资源组合，包括接触到具有广泛基因分型的肿瘤的大量患者群体、已建立的生物库、最先进的临床基因组学能力和专家生物信息学。在具有互补技能的三名经验丰富的主要研究人员的领导下，该教派财团准备执行一种新的早期实验性治疗临床试验范例，目标是验证正确的路径，使用正确的药物瞄准这些路径，并在正确的患者中测试这些药物。 相关性：早期肿瘤学临床试验传统上侧重于确定II期开发的最大耐受量。新靶向药物的最新发展需要一种不同的方法，包括：1)在分子谱人群中进行测试；2)评估中间生物终点；以及3)确定第二阶段研究的最佳生物剂量。

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.