PHASE I TRIALS OF ANTICANCER AGENTS

描述：（申请人的描述）新的 临床试验中的药物治疗仍然是 临床肿瘤学研究的重要领域。 为了确保继续 癌症患者护理和治疗的进展，研究人员 将需要建立在现有的治疗方法， 在这些方案中引入新的药剂和方法。 为新 药物通过早期临床试验进展顺利， 他们应该在及时可靠的研究中心进行评估， 提供最多的临床信息a B 治疗的特征和毒性、药理学和相关 生物学终点 该提案将概述 研究者利用霍普金斯肿瘤科的设施和资源 中心进行高质量的科学基础的I期临床和 新药物在实体瘤患者中的药理学研究， 血液恶性肿瘤。 建议的试验的具体目标如下：1）确定 最大耐受剂量和适当的剂量和时间表， II期研究中的疗效评价。 急性和慢性 将对毒性进行评价和定量。 毒性可能被重新定义 当药剂与其它治疗药物或药剂联合给药时 例如集落刺激因子或其它能够修饰 毒性 2)为了进行详细的药理学研究， 研究中治疗药物的药代动力学和药效学 并在可能的情况下探索特殊患者的这些特征， 人群，如受损的终末器官功能，或评估 基于年龄、性别或种族和民族的差异。 3)到 纳入辅助实验室研究， 患者材料或与临床研究平行进行， 加强对毒性或生物化学和分子生物学的了解， 药物作用机制，以及给药与 和生物学变化。 每项任务的执行都需要自己的专业知识， 重要的是要把它们放在一起考虑。 该提案将详细说明 元素，因为他们存在于约翰霍普金斯执行这项工作。

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.