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。第一阶段 社区将面临巨大的挑战，做出快速、准确的药物开发决定， 由于用于持续临床开发的资源有限，以及潜在的独特概况， 临床候选药物可能会出现。重要的是要积极主动，预见到许多挑战。 最大限度地利用知识库和整合资源，以协助克服其中的许多挑战 将是继续取得成功的关键组成部分。卡马诺斯癌症研究所(KCI)和马里兰大学 Marlene和Stewart Greenebaum癌症中心(UMGCC)联合提交了这份提案，以最大限度地 我们作为一期财团的优势。这两个机构的综合专业知识将我们定义为 药代动力学(PK)、药效学(PD)、成像和生物统计学方面的课程，均为必修课 有效和有效的第一阶段方案的组成部分。这两个机构都认识到 需要了解与肿瘤相关的靶向药物效应。卢鲁索博士(KCI首席调查员)和 索斯维尔(UMGCC首席调查员)都参与了对PD影响的几种不同的探索 代理的类别。索斯维尔博士在密歇根州立大学建立了一个PD翻译研究实验室，以帮助 进一步开发精选的PD终点，以便在该联盟将进行的临床试验中实施。 洛鲁索博士和索斯维尔博士的专业知识结合在一起，使他们在 临床前和临床癌症药物开发。他们的努力导致了几个 商业上可获得的或最近提交的药物，包括VELCADE？，Ontak？，Capecitabine，zoledronic acid， 吉非替尼、拉帕替尼和依沙比平，仅举几例。他们的项目已经认识到患者资源 是有价值和有限的，并已成功地开发和评估了新的试验设计，以 尽量减少无效剂量治疗的患者。这两个机构的地理位置都适合为他们服务 拥有大量女性和少数民族基础的市中心人口，为特殊人口提供了潜力 学习。希尔兹博士，我们在KCI的合作者，一直是PET成像领域的思想领袖，拥有几种示踪剂， 包括FDG和FFT，到他的投资组合中。这种面向成像的能力是另一项独特的功能 可供他的财团使用。随着这两个项目的持续增长和扩大，我们感受到了这一点 协作将为通过以下方式提供的新型代理的持续开发做好准备 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.