Early Clinical Trials of New Anti-Cancer Agents

描述(申请人提供)：在未来十年内，将有大约500种抗癌药物可用于开发。第一阶段社区将面临巨大的挑战，做出快速、准确的通过/不通过药物开发决定，这是因为用于持续临床开发的资源有限，以及临床候选药物可能展现的潜在的独特情况。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库和整合资源，以协助克服其中许多挑战，将是继续取得成功的一个关键组成部分。卡马诺斯癌症研究所(KCI)和马里兰大学Marlene&Stewart Greenebaum癌症中心(UMGCC)联合提交了这份申请，以最大限度地发挥我们作为第一阶段联盟的优势。这两家机构的综合专业知识使我们成为药物动力学(PK)、药效学(PD)、成像和生物统计学领域的思想领导者，这些都是有效和有效的第一阶段计划的所有必要组成部分。这两个机构都认识到更有必要了解与肿瘤相关的靶向药物效应。洛鲁索博士(KCI首席研究员)和索斯维尔博士(UMGCC首席研究员)都参与了对几种不同类别药物的PD效应的探索。索斯维尔博士在UMGCC建立了PD转化研究实验室，以帮助进一步开发选定的PD端点，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，在临床前和临床癌症药物开发方面提供了至少40年的经验。他们的努力导致了几种商业上可用的或最近提交的药物的开发，包括VELCADE？1/2、Ontak？1/2、Capecitabine、zoledronic acid、Gefitinib、Lapatanib和ixabpione，仅举几例。他们的计划已经认识到患者资源是宝贵的和有限的，并在开发和评估新的试验设计方面取得了重大成功，以最大限度地减少无效剂量治疗的患者。这两个机构的位置都适合为拥有大量妇女和少数民族基础的市中心人口提供服务，为专门的人口研究提供了潜力。希尔兹博士是我们在KCI的合作者，他一直是PET成像领域的思想领袖，他的投资组合中有几种示踪剂，包括FDG和Flt。这种面向成像的能力是他的财团可用的另一个独特功能。随着这两个项目的持续增长和扩大，我们认为这一合作将为通过国家癌症研究所的癌症治疗评估项目提供的新型药物的继续开发奠定良好的基础。

DESCRIPTION (provided by applicant): 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 development decisions, due to limited resources for 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 application to maximize our strengths as a Phase I Consortium. The combined expertise of both institutions define us as thought leaders 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 UMGCC to help further develop select PD endpoints for implementation in the clinical trials to be pursued by this consortium. 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¿1/2, Ontak¿1/2, 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.