Phase I Clinical Trials of Novel Anticancer Agents

新型抗癌药物的I期临床试验

• 批准号: 7021408
• 负责人: CHANDRA BELANI
• 金额: $ 42.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-18 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7021408
• 关键词: antineoplastics; apoptosis; clinical research; clinical trial phase I; colony stimulating factor; combination chemotherapy; cooperative study; dosage; drug administration rate /duration; drug adverse effect; drug metabolism; drug screening /evaluation; human subject; immunocytochemistry; immunoprecipitation; in situ hybridization; neoplasm /cancer chemotherapy; patient oriented research; pharmacokinetics; terminal nick end labeling; tubulin; western blottings

DESCRIPTION (provided by applicant): This grant application is based on the premise that characterization and understanding of an antineoplastic agent's pharmacology should allow better clinical utilization of that agent. Impeccable characterization of the clinical toxicities and maximum tolerated dose (MTD) of an agent is no longer sufficient. Ideally, an agent's pharmacologic characteristics--including its pharmacokinetics, metabolism, and pharmacodynamic manifestations on the molecular, cellular, and clinical levels--would be defined during early clinical trials. This pharmacologically-based approach will promote the performance of scientifically directed, phase I trials that integrate information regarding the mechanisms of action and pharmacodynamic consequences of NCl anti-cancer agents into their design. There will be continued characterization of novel tubulin-interactive agents, and the studies involving texaphyrin-based photodynamic and radiation-sensitizing agents will be extended. In addition to cytotoxic agents, other agents with novel mechanisms, including antiangiogenesis agents, differentiating agents, apoptosis-inducing agents, anti-sense oligonucleotides, and related gene-specific therapies will be evaluated. Agents whose pharmacology has been well characterized by the UPCl investigators, under the umbrella of the NCl-sponsored contract "Preclinical Studies of Antitumor and Anti-HIV Agents," will be further explored in phase I studies. The UPCl will continue to assume a leadership role in the study of antineoplastic agents for specific groups of patients (i.e., those with hepatic or renal dysfunction). Additional evaluation of mechanistic aspects and correlative science studies will be incorporated into phase I studies of novel agents. This application reflects the areas of interest and documented expertise of the investigators in conducting phase I trials. The commitment of the UPCl and the facilities described convincingly demonstrates that these studies can be successfully completed. It is hoped that these approaches will allow for better understanding of how these agents can be optimally utilized in clinical practice.

描述（由申请人提供）：本拨款申请的前提是抗肿瘤药药理学的表征和理解应有助于该药物更好的临床利用。药物的临床毒性和最大耐受剂量 (MTD) 的完美表征已不再足够。理想情况下，药物的药理学特征——包括其在分子、细胞和临床水平上的药代动力学、代谢和药效学表现——将在早期临床试验中确定。这种基于药理学的方法将促进科学指导的 I 期试验的进行，这些试验将有关 NCl 抗癌药物的作用机制和药效学后果的信息整合到其设计中。将继续对新型微管蛋白相互作用剂进行表征，并且将扩展涉及基于泰克萨菲林的光动力剂和辐射敏化剂的研究。除了细胞毒性药物外，还将评估具有新机制的其他药物，包括抗血管生成剂、分化剂、细胞凋亡诱导剂、反义寡核苷酸和相关基因特异性疗法。在NCI赞助的合同“抗肿瘤和抗HIV药物的临床前研究”的框架下，UPCl研究人员已经很好地表征了其药理学特征的药物，将在第一阶段研究中进一步探索。 UPCl 将继续在针对特定患者群体（即肝或肾功能障碍患者）的抗肿瘤药物研究中发挥领导作用。对机制方面和相关科学研究的额外评估将纳入新药的第一阶段研究中。该应用程序反映了研究人员在进行第一阶段试验时感兴趣的领域和记录的专业知识。 UPCl 的承诺和所描述的设施令人信服地表明这些研究可以成功完成。希望这些方法能够更好地理解如何在临床实践中最佳地利用这些药物。