Phase I Molecular and Clinical Pharmacodynamic Trials ETCTN

 描述(申请人提供)：此次修订我们的UM1合作协议的目的是通过将第二阶段临床试验计划与目前专注于第一阶段临床试验的实验治疗临床试验网络(ETCTN)合并，加强NCI支持的实验性癌症治疗的早期开发。加州癌症联盟(CCC)由希望之城综合癌症中心(COH)、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，并将在我们的UM1中加入斯坦福大学癌症中心(AO)。CCC将把我们广泛的第二阶段临床试验计划(目前通过NCI合同“N01”提供资金)整合到一个参与ETCTN的单一管理结构中。我们的多学科研究团队将联合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、细胞周期调节、非侵入性成像和生物信息学领域的专业知识，为ETCTN药物特定跨网络药物开发“项目组”做出贡献，以进行创新的、以实验室为指导的早期发育和药物动力学研究。我们建议利用UCD、COH、USC和SU的患者和科学资源和专业知识来实现以下具体目标：(目标1)快速设计、启动和完成实验室驱动的第二阶段临床试验，单独或联合评估NCI赞助的药物的安全性和有效性，以最大限度地利用已建立的具有临床药物开发专业知识的联盟的患者、科学和导师/职业发展资源；(目标2)在第二阶段肿瘤学试验的背景下，采用系统的方法收集、处理和存储血液、正常和肿瘤组织以及其他相关生物样本，用于分子和药理学研究；以及(目标3)利用先进的临床前模型为拟议的试验发展科学基础；评估新疗法(包括免疫疗法)对其分子或生物靶点的生物效应；纳入适当的研究设计、成像和统计方法以评估中间终点；并将结果与第二阶段的临床相关结果相关联。位于LAO的单一数据协调中心目前管理着LAO和所有由NCI赞助的第一阶段试验(根据当前的UM1)和第二阶段试验(根据当前的N01合同)的参与(临床试验管理、患者积累以及与多个NCI部门和工作人员的沟通)，这将使当前的CCC第二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.