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; 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）：此赠款申请基于以下前提：对抗塑料药理学的表征和理解应允许更好地临床利用该药物。对药剂的临床毒性和最大耐受剂量（MTD）的无可挑剔的表征不再足够。理想情况下，在早期临床试验期间，将定义药物的药理特征 - 包括其药代动力学，代谢和药效学表现 - 在早期临床试验中应定义。这种基于药理的方法将促进科学定向的，I期试验的性能，该试验整合了有关NCL抗癌药物的作用机理和药效动力学后果的信息。新型微管蛋白相互作用剂将继续表征，并将扩展涉及基于质法磷酸纤维蛋白的光动力和辐射敏感剂的研究。除了细胞毒性剂外，还将评估具有新机制的其他新型机制，包括抗血管生成剂，分化剂，凋亡诱导的剂，抗敏感性寡核苷酸以及相关的基因特异性疗法。在NCL赞助的合同“抗肿瘤和抗HIV药物的临床前研究”的保护下，将在I阶段研究中进一步探讨了药理学的特征。 UPCL将继续在针对特定患者组（即患有肝或肾功能障碍的患者组）的抗肿瘤剂研究中发挥领导作用。机械方面和相关科学研究的其他评估将纳入新型药物的I期研究中。该申请反映了在进行I期试验中，研究人员感兴趣的领域和记录的专业知识。 UPCL和所描述的设施的承诺令人信服地表明，这些研究可以成功完成。希望这些方法能够更好地了解如何在临床实践中最佳利用这些代理。