Early Clinical Trials of New Anti-Cancer Agents

描述（由申请人提供）：在未来十年内，将有大约500种抗癌药物可供开发。由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独特特征，I期社区将面临快速准确的go/no go药物开发决策的重大挑战。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。Karmanos癌症研究所（KCI）和马里兰州大学Marlene & Stewart Greenebaum癌症中心（UMCCC）联合提交了此申请，以最大限度地发挥我们作为I期联盟的优势。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思想领袖，这些都是高效和有效的I期项目的必要组成部分。这两个机构都认识到更需要了解肿瘤相关的靶向药物作用。LoRusso博士（KCI主要研究者）和Sausville博士（UMCCC主要研究者）都参与了几种不同类型药物的PD效应探索。Sausville博士在UMCCC建立了一个PD转化研究实验室，以帮助进一步开发选择PD终点，以便在该联盟追求的临床试验中实施。LoRusso博士和Sausville博士的综合专业知识在临床前和临床癌症药物开发方面共同提供了至少40年的经验。他们的努力导致了几种市售或最近提交的药物的开发，包括万珂1/2、昂他克1/2、卡培他滨、唑来膦酸、吉非替尼、拉帕替尼和伊沙匹隆，仅举几例。他们的项目已经认识到患者资源是有价值的和有限的，并且在开发和评估新的试验设计方面取得了重大成功，以尽量减少无效剂量治疗的患者。这两个机构的地点都适合为有大量妇女和少数民族的内城人口提供服务，为特殊人口研究提供了可能。Shields博士，我们在KCI的合作者，一直是PET成像的思想领袖，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的功能。随着这两个项目的持续发展和扩大，我们认为这种合作将有利于通过国家癌症研究所的癌症治疗评估项目继续开发新的药物。

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.