Early Clinical Trials of New Anti-Cancer Agents

在未来十年内，将有大约500种抗癌药物可供开发。I期 社区将面临重大挑战，迅速准确地做出药物开发的决定， 由于持续临床开发的资源有限， 临床候选药物可能会展开。重要的是要积极主动，预见到许多挑战。 最大限度地扩大知识基础，整合资源，以协助克服其中许多挑战 将是持续成功的关键组成部分。Karmanos癌症研究所（KCI）和马里兰州大学 Marlene和Stewart Greenebaum癌症中心（UMCCC）联合提交了这份提案， 我们作为第一阶段联盟的优势这两个机构的综合专业知识使我们认为， 药代动力学（PK）、药效学（PD）、成像和生物统计学方面的领先者，所有必要的 第一阶段计划的组成部分。这两个机构都认识到， 需要了解肿瘤相关的靶向药物作用。Drs. LoRusso（KCI主要研究者）和 Sausville（UMCCC首席研究员）都涉及探索几种不同的PD效应 代理人的类。Sausville博士在UMGC建立了一个PD转化研究实验室， 进一步开发选定的PD终点，以便在本联盟开展的临床试验中实施。 LoRusso博士和Sausville博士的综合专业知识共同提供了至少40年的经验， 临床前和临床癌症药物开发。他们的努力导致了几个 市售的或最近提交的试剂，包括万珂、Ontak、卡培他滨、唑来膦酸， 吉非替尼、拉帕替尼和伊沙匹隆等。他们的项目已经认识到， 是有价值的和有限的，并取得了显着的成功，开发和评估新的试验设计， 尽量减少无效剂量治疗的患者。这两个机构的位置都有助于服务 有大量妇女和少数民族的内城人口，为特殊人口提供了潜力 问题研究Shields博士，我们在KCI的合作者，一直是PET成像的思想领袖，有几种示踪剂， 包括FDG和FLT，到他的投资组合。这种面向成像的能力是一个额外的独特功能 提供给他的财团随着这两个项目的持续增长和扩大，我们感到， 合作将有利于继续开发通过 国家癌症研究所的癌症治疗评估计划。

Roughly 500 anti-cancer agents will be available for development within the next decade. The Phase I community will face significant challenges making swift and accurate go/no go drug developmentdecisions, due to limited resourcesfor continued clinical development as well as potentially unique profiles that the clinical drug candidates may unfold. It is important to be proactive, anticipating many of the challenges. Maximizing the knowledge base and combining resources to assist in overcoming many of these challenges will be a key component of continued success. Karmanos Cancer Institute (KCI) and University of Maryland Marlene & Stewart Greenebaum Cancer Center(UMGCC)jointly are submitting this proposal to maximize our strengths as a Phase I Consortium. The combined expertise of both institutions define us asthought eaders in pharmacokinetics (PK), pharmacodynamics (PD), imaging and biostatistics, all necessary components of an efficient and effective phase I program. Both institutions have recognized the greater need for understanding tumor-related targeted drug effects. Drs. LoRusso (KCI Principal Investigator) and Sausville (UMGCC Principal Investigator) have both involved exploration of PD effects of several different classes of agents. Dr. Sausville has developed a PD translational research laboratory at UMGCCto help further develop select PD endpoints for implementation in the clinical trials to be pursued by thisconsortium. The combined expertise of Drs. LoRusso and Sausville lend collectively at least 40 years experience in preclinical and clinical cancer drug development. Their efforts have led to the development of several commercially available or recently filed agents, including Velcade¿, Ontak¿, capecitabine, zoledronic acid, gefitinib, lapatanib, and ixabepilone, to name a few. Their programs have recognized that patient resources are valuable and limited, and have had significant success developing and evaluating novel trial designs to minimize patients treated at ineffective doses. The locations of both institutions lend themselves to service inner city populations with large women and minority bases, offering the potential for special population studies. Dr. Shields, our collaborator at KCI, has been a thought leader in PET imaging, with several tracers, including FDG and FLT, to his portfolio. This imaging oriented capacity is yet an additional unique feature available to his consortium. With the continued growth and expansion of both programs, we feel this collaboration will be well positioned for the continued development of novel agents offered through the Cancer Treatment Evaluation Program at the National Cancer Institute.