Phase I Molecular and Clinical Pharmacodynamic Trials ETCTN

 描述（由申请人提供）：本次UM 1合作协议修订的目的是通过将2期临床试验项目与目前专注于1期临床试验的实验性治疗药物临床试验网络（ETCTN）合并，加强NCI支持的实验性癌症治疗药物的早期开发。加州癌症联盟（CCC）由希望之城综合癌症中心（COH，“牵头学术组织”，[LAO]）、加州大学戴维斯癌症中心（UCD，附属组织[AO]）和南加州大学（USC）/诺里斯综合癌症中心（USC，AO）组成，并将在UM 1中添加斯坦福大学癌症中心（AO）和本修订版。CCC将把我们广泛的2期临床试验计划（目前通过NCI合同“N 01”资助）整合到一个参与ETCTN的单一管理结构中。我们的多学科研究人员小组将有助于ETCTN代理特定的跨网络药物开发“项目团队”从COH，UCD，USC和SU在分子药理学，药代动力学，药效学，药物基因组学，信号转导，细胞周期调控，非侵入性成像和生物信息学领域的综合专业知识进行创新，实验室指导的早期开发和药代动力学研究。我们建议利用UCD，COH，USC和SU的综合患者和科学资源和专业知识来实现以下具体目标：（目的1）快速设计、启动和完成实验室驱动的II期临床试验，评估NCI申办的药物单独或联合使用的安全性和有效性，以最大限度地提高患者、科学、以及在临床药物开发方面具有专业知识的成熟联盟的指导/职业发展资源;（目的2）采用系统的方法来收集、处理和储存血液、正常和肿瘤组织，和其他相关的生物样品，用于2期肿瘤学试验背景下的分子和药理学研究;以及（目标3）为使用先进的临床前模型的拟议试验制定科学依据;评估新疗法的生物效应（包括免疫疗法）的分子或生物学靶点;纳入适当的研究设计、成像和统计方法，以评估中间终点;并将结果与II期临床相关结局相关联。位于LAO的单一数据协调中心目前管理参与由LAO和所有CCC AO为两项NCI-Sponsored I期试验（临床试验管理、患者招募以及与多个NCI部门和工作人员的沟通）（根据当前UM 1）和II期试验（根据目前的N 01合同），这将使目前的CCC第2阶段计划无缝地纳入ETCTN结构。

 DESCRIPTION (provided by applicant): The purpose of this Revision to our UM1 Cooperative Agreement is to enhance the NCI-supported early development of experimental cancer therapeutics by merging the Phase 2 clinical trials program with the Experimental Therapeutics Clinical Trials Network (ETCTN) that is currently focused on Phase 1 clinical trials. The California Cancer Consortium (CCC) consists of the City of Hope Comprehensive Cancer Center (COH, the "Lead Academic Organization," [LAO]), the University of California, Davis Cancer Center (UCD, Affiliated Organization [AO]), and the University of Southern California (USC)/Norris Comprehensive Cancer Center (USC, AO) and will add Stanford University Cancer Center (AO) with this Revision to our UM1. The CCC will integrate our extensive Phase 2 clinical trials program (currently funded through an NCI contract, "N01") into a single administrative structure participating in the ETCTN. Our multidisciplinary group of investigators will contribute to ETCTN agent-specific trans-network drug development "Project Teams" from the combined expertise of COH, UCD, USC, and SU in the areas of molecular pharmacology, pharmacokinetics, pharmacodynamics, pharmacogenomics, signal transduction, cell cycle regulation, non-invasive imaging, and bioinformatics to conduct innovative, laboratory-directed early phase developmental and pharmacokinetic studies. We propose to utilize the combined patient and scientific resources and expertise of UCD, COH, USC, and SU to accomplish the following Specific Aims: (Aim 1) to rapidly design, initiate and complete laboratory-driven Phase 2 clinical trials evaluating the safety and efficacy of NCI-sponsored agents, alone or in combination, in order to maximize the patient, scientific, and mentorship/career development resources of an established Consortium with demonstrated expertise in clinical drug development; (Aim 2) to employ a systematic approach to collection, processing, and storage of blood, normal and tumor tissue, and other relevant biologic samples for molecular and pharmacologic studies in the context of Phase 2 oncology trials; and (Aim 3) to develop scientific rationale for proposed trials using advanced preclinical models; to evaluate biologic effects of novel therapeutics (including immunotherapy) on their molecular or biologic targets; to incorporate appropriate study designs, imaging, and statistical methods for assessment of intermediate endpoints; and to correlate findings with clinically relevant outcomes in the Phase 2 setting. A single Data Coordinating Center located at the LAO currently manages participation (clinical trial management, patient accrual, and communication with multiple NCI components and staff) by the LAO and all CCC AOs for both NCI-Sponsored Phase 1 trials (under the current UM1) and Phase 2 trials (under the current N01 contract), which will make the incorporation of the current CCC Phase 2 program into the ETCTN structure seamless.