PHASE I TRIALS OF ANTICANCER AGENTS

描述：(申请人的描述)介绍新的 进入临床试验的抗肿瘤疗法仍然是最多的 临床肿瘤学的重要研究领域。以确保继续 癌症患者护理和治疗的进展，调查人员 将需要建立在现有治疗方法的基础上 在这些计划中引入新的代理和模式。对于新的 药物顺利通过早期临床试验势在必行 在中心进行评估，在那里可以进行及时和可靠的研究 为临床提供了最大的信息 该疗法的特点和毒性、药理学和相关 生物终点。这项提案将概述 研究人员利用霍普金斯肿瘤学的设施和资源 中心将高质量地开展以科学为基础的I期临床和 实体瘤患者新药的药理学研究 恶性血液病。 建议的试验的具体目的如下：1)界定 最大耐受剂量和适当的剂量和时间表 第二阶段研究中的疗效评价。急慢性疾病 毒性将进行评估和量化。毒性可以重新定义 当药物与其他治疗药物或药物联合给药时 例如菌落刺激因子或其他能够修饰 毒性。2)进行详细的药理学研究， 正在研究的治疗药物的药代动力学和药效学 并尽可能探讨特殊患者的这些特征 如终端器官功能受损的人群，或评估 基于年龄、性别或种族和民族的差异。3)至 纳入在临床上进行的辅助实验室研究 患者资料或与以下临床研究平行进行 加强对毒性或生化和分子方面的认识 药物作用机制及其与药物给药的关系 以及接受治疗的患者的生物学变化。 执行这些任务中的每一个都需要自己的专业知识，但它 重要的是要把它们放在一起考虑。这项提案将详细说明 约翰霍普金斯大学存在的元素来执行这项工作。

DESCRIPTION: (Applicant's Description) The introduction of new antineoplastic therapies into clinical trials remains one of the most important areas of investigation in clinical oncology. To assure continued progress in the care and treatment of patients with cancer, investigators will need to build on the existing therapeutic approaches by the introduction of new agents and modalities into these programs. For new agents to progress smoothly through early clinical trials it is imperative that they be evaluated in centers where timely and reliable studies can be performed which provide maximum information a b o u t the clinical characteristics and toxicities of the therapy, pharmacology, and relevant biologic endpoints. This proposal will outline the capability of the investigators utilizing the facilities and resources of the Hopkins Oncology Center to perform high quality scientifically based phase I clinical an pharmacologic studies of new agents in patients with solid tumors and hematologic malignancies. The specific aims of the trials proposed are as follows: 1) To define the maximum tolerated dose and an appropriate dose and schedule for further evaluation of efficacy in phase II studies. The acute and chronic toxicities will be evaluate and quantitated. Toxicities may be redefined when agents are given in combination with other therapeutic drugs or agents such as colony stimulating factors or other agents capable of modifying toxicity. 2) To p e r f orm detailed studies of the pharmacology, pharmacokinetics, and pharmacodynamics of the therapeutic agents under study and when possible to explore these characteristics in special patient populations such as impaired end organ function, or to evaluate for differences based on age, gender, or race and ethnic group. 3) To incorporate ancillary laboratory studies which are performed on clinical patient material or performed in parallel to the clinical studies which enhance the understanding of toxicity or biochemical and molecular mechanisms of drug effect, and the relationship between drug administration and biological changes in treated patients. Performance of each of these tasks requires an expertise of its own but it is important they be considered together. This proposal will detail the elements as they exist at Johns Hopkins to perform this work.