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的数据爆炸。虽然这些进展使几种难治性恶性肿瘤的治疗取得了重大改进，但大多数晚期癌症仍然无法治愈。西南早期临床试验（SECT）联盟由得克萨斯大学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，在广泛的患者人群中领导，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型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分析，以根据已识别的分子畸变（如适用）优化每例患者的潜在相关治疗选择。3.开发临床相关的药效学反应标志物。4.指导初级教师，学员和研究人员（如适用）领导，执行，分析和报告ET-CTN和其他临床试验。5.在ET-CTN内提供科学和行政领导，包括积极参与项目团队，研究设计和方案制定，网络组出版物的作者/合著者，以及参与科学，行政或特设委员会，以及参与NCI中央IRB和出席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的成熟能力外，SECT机构还拥有无与伦比的资源组合，包括获得大量具有广泛基因型肿瘤的患者群体、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。由三位经验丰富的具有互补技能的主要研究者领导，SECT联盟准备执行早期实验性治疗临床试验的新范式，目标是验证正确的途径，用正确的药物靶向这些途径，并在正确的患者中测试这些药物。 相关性：早期肿瘤临床试验传统上侧重于确定II期开发的最大耐受剂量。新型靶向药物的最新发展需要不同的方法，包括：1）在分子特征人群中进行测试; 2）评价中间生物学终点; 3）确定II期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.