Phase I Clinical Trials of Novel Anticancer Agents

新型抗癌药物的I期临床试验

• 批准号: 6581593
• 负责人: CHANDRA BELANI
• 金额: $ 40.35万
• 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/6581593
• 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)：这项资助申请是基于这样一个前提，即对抗肿瘤药物的药理学的描述和理解应该允许该药物更好地在临床上使用。一种药物的临床毒性和最大耐受量(MTD)的无懈可击的特征不再足够。理想情况下，一种制剂的药理学特征--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第一阶段试验的表现，这些试验将NCL抗癌剂的作用机制和药效学结果的信息整合到它们的设计中。新的微管蛋白相互作用剂的特性将继续得到表征，涉及以纹藻蛋白为基础的光动力和辐射敏感剂的研究将会扩大。除细胞毒性药物外，还将评估其他具有新机制的药物，包括抗血管生成药物、分化药物、凋亡诱导剂、反义寡核苷酸和相关的基因特异性治疗。在NCL赞助的合同“抗肿瘤和抗艾滋病毒药物的临床前研究”的框架下，其药理学已被UPCL调查人员很好地描述的药物，将在第一阶段研究中进一步探索。UPCL将继续在特定患者组(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。对机械方面的额外评估和相关的科学研究将纳入新药的第一阶段研究。该申请反映了调查人员在进行第一阶段试验时感兴趣的领域和记录在案的专门知识。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这些药物如何在临床实践中得到最佳利用。