PHASE I TRIALS OF ANTICANCER AGENTS

描述：（申请人的描述）在本申请中， 俄亥俄州州立大学综合大学基础科学研究员 癌症中心（OSUCCC）联合起来，以合作的方式， 开展新的癌症治疗药物和方案的I期试验。 这些研究人员将与癌症治疗密切合作 美国国立癌症研究所相关研究的评估计划 它将在基础科学的背景下评估临床结果 意见。 目前的建议建立在OSUCCC的优势之上 进行相关生物测量的临床试验。 试验 根据该提案进行的研究将强调那些药物和方案， OSUCCC的哪些教员先前具有临床前经验和/或 申请人认为其影响细胞和分子 在他们的实验室里研究网络。 缩肽的选择和 软海绵素B用于拟定的I期试验反映了这些考虑。 因此，这两种药物的相关研究涉及药物动力学 细胞凋亡和信号转导， 微管和拓扑异构酶实验室在体内和体外 测量. 其他I期试验将利用DNA修复，生物学 反应调节剂、免疫反应、药效学和癌症 化学预防实验室，视情况适用于新制剂或新用药方案 和调查。 药代动力学将在以下方面发挥核心作用 临床和生物学终点的解释。 数据管理和 通过计算机化数据和前瞻性研究， 方案管理系统在临床实践中的价值 审判 可用于I期试验的患者数量， 临床和基础科学合作研究经验和专业知识 这一建议的参与者提供了一个有效的手段，使新的 更快地将抗癌药物输送给癌症患者。 在此基础上进行的研究 该提案不仅将推动新疗法从实验室走向临床， 还将为癌症生物学提供新的见解。 这些见解反过来 将导致更合理的抗癌治疗。

DESCRIPTION: (Applicant's Description) In this application clinical and basic science investigators of The Ohio State University Comprehensive Cancer Center (OSUCCC) join together in a collaborative approach to the conduct of phase I trials of new cancer therapeutic agents and regiments. These investigators will cooperate closely with the Cancer Therapy Evaluation Program of the National Cancer Institute in correlative studies which will evaluate clinical outcomes in the context of basic science observations. The present proposal builds upon the strengths of the OSUCCC in conducting clinical trials with pertinent biologic measurements. Trials conducted under this proposal will emphasize those agents and regimens with which faculty of the OSUCCC have had prior preclinical experience and/or which the applicants identify as impacting on the cellular and molecular network under study in their laboratories. The choice of depsipeptide and halichondrin B for proposed phase I trials reflect those considerations. Thus, correlative studies for those two drugs involve t h e p harmacokinetic and pharmacoanalytic, the apoptosis and signal transduction, the microtubule, and the topoisomerase laboratories in in vivo and in vitro measurements. Other phase I trials will utilize the DNA repair, biological response modifier, immune response, pharmacodynamic, and cancer chemoprevention laboratories as appropriate for the new agent or regiment u n d er investigation. Pharmacokinetics will play a central role in interpretation of clinical and biologic end points. Data management and protocol compliance is enhanced by; computerized data and prospective protocol management system of proven value in the conduct of clinical trials. Patient numbers available for phase I trials coupled with the clinical and basic science collaborative research experience and expertise of this proposal's participants provide an effective means for bringing new cancer agents more rapidly to the cancer patient. Studies done under this proposal not only will advance new therapies from the bench to the bedside, but also will provide insights into cancer biology. These insights in turn will lead to more rational anticancer treatment.