PHASE II TRIALS OF NEW ANTICANCER AGENTS

本提案的主要长期目标是批判性地评估 在临床上，用于一系列人类恶性肿瘤的新疗法。这将 通过科学地执行高质量的第二阶段来完成- 新抗癌疗法的指导性试验。 这项建议是 旨在联合收割机和集中广泛的资源，经验和 广泛的临床和实验室研究者的能力 在约翰霍普金斯肿瘤中心。这将是完成 因为有许多关键的优势， 由提案协调。其中包括：（1）一个大的主动多... 强调新药开发的学科临床研究计划， 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)广泛的实验室项目，如肿瘤遗传学， 药理学、耐药性、肿瘤免疫学和基因治疗， 造血、骨髓移植、程序性细胞死亡与肿瘤 与临床程序直接相关的转移，（3）异常 临床试验设计、统计学和数据管理方面的专业知识;（4） 在设计和实施创新的 将新疗法与封闭实验室相结合的治疗试验 相关性该提案通过定义一个 组织结构将：（1）促进最佳研究设计 通过早期阶段生物统计学和药理学核心的输入 方案设计，（2）纳入专家科学核心进行审查， 评估、修改和选择方案以提交给CTEP， （3）监督并确保严格遵守RFA准则， 招募目标、方案合格性、质量控制、研究监查和 数据收集、管理和分析。提交了三份协议 这个提议。这反映了应用程序的优势。这些 包括拓扑替康在成人ALL中的研究， 拓扑异构酶和多药耐药水平，紫杉醇和 环磷酰胺在乳腺癌妇女组织活检中的作用， 评估耐药机制和新生霉素逆转 转移性乳腺癌患者的烷化剂耐药性 正在接受大剂量化疗

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.