PHASE II TRIALS OF NEW ANTICANCER AGENTS

新型抗癌药物的二期试验

• 批准号: 2105286
• 负责人: Ross C Donehower
• 金额: $ 29.42万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-13 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2105286
• 关键词: DNA topoisomerases; antineoplastics; apoptosis; bone marrow transplantation; breast neoplasms; clinical trials; cooperative study; cyclophosphamide; data collection; drug screening /evaluation; gastrointestinal neoplasms; gene therapy; hematopoiesis; human subject; human therapy evaluation; lung neoplasms; metastasis; multidrug resistance; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer pharmacology; novobiocin; paclitaxel; pharmacokinetics; statistics /biometry

The primary long term objective of this proposal is to critically evaluate in the clinic novel therapies for a range of human malignancies. This will be accomplished by performing high quality Phase II scientifically- directed trials with novel anti-cancer therapies. This proposal is designed to combine and focus the extensive resources, experience and capabilities of a broad range of.clinical and laboratory investigators within the Johns Hopkins Oncology Center. This will be accomplished because of a number of critical strengths which will be effectively coordinated by the proposal. These include (l) a large active multi- disciplinary clinical research program emphasizing new drug development, breast cancer, aerodigestive tract-tumors, bone marrow transplantation, lung cancer, leukemia, gastrointestinal and genitourinary malignancies, (2) a broad range of laboratory programs in areas such as tumor genetics, pharmacology, drug resistance, tumor immunology and gene therapy, hematopoiesis, marrow transplantation, programmed cell death and tumor metastasis which relate directly to the clinical programs, (3) exceptional expertise in clinical trial design, statistics and data management and (4) a proven track record in the design and implementation of innovative therapeutic trials combining novel treatments with close laboratory correlations. This proposal augments these strengths by defining an organizational structure which will, (1) facilitate optimal study design by input from the Biostatistics and Pharmacology Cores at an early stage of protocol design, (2) incorporate an expert Scientific Core to review, evaluate, modify and select protocols for submission to CTEP under this mechanism and, (3) monitor and ensure strict adherence to RFA guidelines, accrual goals, protocol eligibility, quality control, study monitoring and data collection, management and analysis. Three protocols are submitted with this proposal. which reflect the strengths of the application. These comprise a study of topotecan in adult ALL with analysis of leukemia cell topoisomerase and MDR levels, a trial of the combination of taxol and cyclophosphamide in women with breast cancer with tissue biopsies to evaluate mechanisms of resistance and a study of novobiocin to reverse alkylating agent drug resistance in women with metastatic breast cancer undergoing high-dose chemotherapy.

该提案的主要长期目标是批判性地评估 在临床上针对一系列人类恶性肿瘤的新疗法。这将 通过科学地进行高质量的第二阶段来完成 新型抗癌疗法的定向试验。 这个提议是 旨在结合和集中广泛的资源、经验和 广泛的临床和实验室研究人员的能力 约翰霍普金斯大学肿瘤中心内。这将实现 由于许多关键优势将有效地 由提案协调。这些包括（l）一个大型有源多 学科临床研究计划强调新药开发， 乳腺癌、呼吸消化道肿瘤、骨髓移植、 肺癌、白血病、胃肠道和泌尿生殖系统恶性肿瘤、 (2) 肿瘤遗传学等领域的广泛实验室项目， 药理学、耐药性、肿瘤免疫学和基因治疗、 造血、骨髓移植、程序性细胞死亡和肿瘤 与临床方案直接相关的转移，（3）异常 临床试验设计、统计和数据管理方面的专业知识以及 (4) 在创新设计和实施方面拥有良好的记录 结合新疗法与密切实验室的治疗试验 相关性。该提案通过定义一个增强了这些优势 组织结构将：(1) 促进优化研究设计 通过早期生物统计学和药理学核心的输入 协议设计，(2) 纳入专家科学核心进行审查， 根据本协议评估、修改和选择提交给 CTEP 的协议 机制，(3) 监督并确保严格遵守 RFA 指南， 应计目标、方案资格、质量控制、研究监测和 数据收集、管理和分析。提交了三个协议 有了这个建议。这反映了应用程序的优势。这些 包括拓扑替康治疗成人 ALL 的研究以及白血病细胞分析 拓扑异构酶和 MDR 水平，紫杉醇和紫杉醇组合的试验 环磷酰胺用于乳腺癌女性并进行组织活检 评估耐药机制以及新生霉素逆转的研究 转移性乳腺癌女性烷化剂耐药性 正在接受大剂量化疗。