Phase I Trials of Anti-Cancer Agents

描述(由申请人提供)：第一阶段研究在开发新的癌症治疗方法方面发挥着关键作用。这些试验是“人类第一”研究的基础研究和临床研究之间的初步接口。成功的治疗研究体现了在这一最初发展的关键时期临床和实验室之间的迭代过程。在过去，第一阶段试验严格地集中于确定新药物的毒性和药代动力学，而现在的重点是在不影响安全和有效给药分析的情况下有效地获得更多的信息。这项任务要求实时获取药代动力学、药效学和药物基因组学，以及细致的临床评估。在这项应用中，俄亥俄州立大学综合癌症中心(OSUCCC)的临床和基础科学研究人员加入了一种合作的方法，对新的癌症治疗药物和方案进行I期试验。研究人员将与国家癌症研究所密切合作，开发相关研究，在基础科学观察的背景下评估临床结果。本建议建立在OSUCCC在使用相关生物测量进行临床试验方面的26年经验和科学实力的基础上。试验的目标将是我们的教员先前具有临床前经验的药物和策略，以及/或他们实验室正在研究的细胞和分子网络。OSUCCC的实验治疗计划在信号转导途径、血管生成、细胞周期控制、选择性诱导肿瘤细胞凋亡、单克隆抗体、分子遗传学、组蛋白修饰、DNA甲基化和其他基本靶向治疗策略方面拥有专业知识。俄亥俄州立大学是世界上致力于跨学科研究的最全面的生物医学研究校园之一。与癌症实验治疗相关的科学家在医学和公共卫生学院、药学学院、生物科学学院、数学和物理学院、兽医学院、工程学学院、牙科学院和护理学院中形成了一个关键群体。最终目标是在人体内进行便捷(但彻底)的剂量发现试验，目的是提供安全有效的新疗法，使恶性疾病患者受益。

DESCRIPTION (provided by applicant): Phase I studies play a critical role in the development of new cancer therapies. These trials are the initial interface between basic and clinical research for "first in human" studies. Successful therapeutic research embodies an iterative process between the clinic and the laboratory during this critical period of initial development. Whereas in the past, phase 1 trials focused strictly upon defining the toxicity and pharmacokinetics of new agents, the current emphasis requires that more information is efficiently procured without compromising the analysis of safe and effective administration. This mandate requires real-time procurement of pharmacokinetics, pharmacodynamics, and pharmacogenomics as well as meticulous clinical assessment. In this application, both clinical and basic science investigators of The Ohio State University Comprehensive Cancer Center (OSUCCC) join in a collaborative approach to conduct phase I trials of new cancer therapeutic agents and regimens. Investigators will cooperate closely with the National Cancer Institute in developing correlative studies to evaluate clinical outcomes in the context of basic science observations. The present proposal builds upon twenty-six years of experience and the scientific strength of the OSUCCC in conducting clinical trials with pertinent biologic measurements. Trials will target agents and strategies with which our faculty has prior preclinical experience and/or cellular and molecular networks under study in their laboratories. The Experimental Therapeutics Program at OSUCCC has expertise in signal transduction pathways, angiogenesis, cell cycle control, selective induction of tumor cell apoptosis, monoclonal antibodies, molecular genetics, histone protein modification, DNA methylation and other basic targeted therapeutic strategies. The Ohio State University represents one of the most comprehensive biomedical research campuses in the world dedicated to interdisciplinary research. Respective scientists associated with experimental therapy of cancer form a critical mass within the Colleges of Medicine and Public Health, Pharmacy, Biological Sciences, Mathematical and Physical Sciences, Veterinary Medicine, Engineering, Dentistry, and Nursing. The ultimate goal is to conduct expedient (yet thorough) dose-finding trials in man with the intention of providing safe and effective new therapy to benefit patients with malignant diseases.