Phase I Clinical Trials of New Anti-Cancer Targeted Ther

新型抗癌靶向药物I期临床试验

• 批准号: 6582114
• 负责人: Michael A Carducci
• 金额: $ 37.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-22 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6582114
• 关键词: age difference; antineoplastics; blood chemistry; clearance rate; clinical research; clinical trial phase I; combination chemotherapy; cooperative study; dosage; drug administration rate /duration; drug adverse effect; drug interactions; drug metabolism; drug screening /evaluation; gender difference; genotype; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; pharmacokinetics; positron emission tomography; racial /ethnic difference

DESCRIPTION (provided by applicant): This proposal is to evaluate promising new therapies for patients with malignant disease in a clinically efficient, regulatory compliant, and scientifically rigorous research environment. Phase I clinical studies of new anti-cancer therapies continue to evolve as basic/ translational research has broadened the targeted opportunities to treat malignant disease. Building upon a strong foundation in the conduct of phase I studies, we have assembled an interactive research team that will use rationally designed clinical trials that will enable expansion and expertise in the molecular/pharmacologic assessment of new drug activity. These trials and assessment methods are designed ultimately to impact on the clinical care of patients diagnosed with cancer. The overall objective of these Phase I studies is to determine the appropriate dose and schedule of experimental agents for further evaluation of efficacy in solid tumor/hematologic malignancies and to characterize the acute and chronic toxicities of these anti-cancer therapies. Our Specific Aims are 1) To conduct Phase I clinical trials of novel anti-cancer agents (alone or in combination) in a timely manner; 2) To perform detailed pharmacokinetic studies of these new agents and to correlate these observations with relevant clinical/biologically sound endpoints; 3) To implement correlative and pharmacodynamic laboratory evaluations in proof of drug mechanism phase I clinical trials and to explore optimal relationships between parameters of drug exposure and biological effects; and 4) To maintain a clinical trial infrastructure that is current and compliant with regulatory standards that assure quality care to patients enrolled on early phase clinical trials. Interdisciplinary teams with clinical and laboratory expertise in the areas of novel cytotoxics, signal transduction inhibitors, gene expression strategies, and antiangiogenesis are in place to fully evaluate these areas. These teams are collaborative and meet regularly to review clinical data and laboratory correlates. Members of these teams are open to multi-institutional working groups in these areas of strength. As targets change over the ensuing years, these groups will remain flexible to expansion and change to other targets of interest. We expect to enroll 50-60 patients/year in order to conduct and complete 2-3 phase I clinical trials/year via this cooperative agreement.

描述（由申请人提供）：该提案是在临床高效，符合法规和科学严格的研究环境中评估针对恶性疾病患者的有希望的新疗法。随着基本/转化研究扩大了治疗恶性疾病的目标机会，新抗癌疗法的I期临床研究继续发展。在I期研究的坚实基础的基础上，我们组建了一个交互式研究团队，该团队将使用合理设计的临床试验，该试验将在新药活性的分子/药理评估中扩展和专业知识。这些试验和评估方法最终设计为影响诊断为癌症患者的临床护理。这些I期研究的总体目的是确定实验剂的适当剂量和时间表，以进一步评估实体瘤/血液学恶性肿瘤的疗效，并表征这些抗癌疗法的急性和慢性毒性。我们的具体目的是1）及时对新型抗癌药（单独或组合）进行I期临床试验； 2）对这些新药物进行详细的药代动力学研究，并将这些观察结果与相关的临床/生物学声学端点相关联； 3）在药物机理证明I期临床试验证明中实施相关和药效实验室评估，并探索药物暴露参数与生物学作用之间的最佳关系； 4）维持临床试验基础设施，该试验基础设施符合当前的监管标准，该标准为参加早期临床试验的患者提供了优质护理。在新型细胞毒素，信号转导抑制剂，基因表达策略和抗血管生成方面具有临床和实验室专业知识的跨学科团队，可以充分评估这些领域。这些团队是协作的，并定期开会以审查临床数据和实验室的相关性。这些团队的成员向这些领域的多机构工作组开放。随着目标在随后的几年中的变化，这些群体将保持灵活性，以扩展并改变到其他感兴趣的目标。我们希望通过此合作协议每年进行50-60名患者/年招募2-3阶段的临床试验。