THERAPEUTICS STUDIES OF PRIMARY CNS MALIGNANCIES

产品说明： 此UOI应用程序的总体目标是为以下方面提供支持 机构联盟进行I期和11项新的临床试验， 原发性中枢神经系统疾病患者的化疗/生物制剂 系统（CNS）肿瘤，并进行辅助实验室研究， 潜在的临床意义。 哈佛/朗伍德脑肿瘤中心 丹娜-法伯癌症研究所试验组，布里格姆和妇女 医院，儿童医院和贝斯以色列医院有一个大的 扩大患者人群，并致力于临床和实验室 原发性脑肿瘤的研究 作为“北美大脑”的一部分， 肿瘤联盟”我们的总体目标是进行I期和II期试验， 新型细胞毒性和生物制剂，特别关注 抗血管生成剂。 虽然圣安东尼奥将作为 作为我们联合体的药理学中心，我们的中心能够 试点实验和/或广泛的单一机构 鉴于我们在以下方面的丰富经验， 基于药理学的I期试验。 由于要研究的特定药剂 在未来四年是未知的，在这个时候，我们选择了发展 建立在我们以前的临床前和临床研究基础上的协议 基于我们的研究，开发了三种具有抗血管生成活性的药物， 对肿瘤相关血管生成的长期兴趣：a.）沙利度胺a 具有抗血管生成活性的致畸镇静剂， 在恶性胶质瘤患者中完成了一项有希望的11期试验： B.）一种新的具有抗血管生成活性的人β-干扰素， 在我们最近完成的阶段中证实了显著的抗胶质瘤活性 I trial; and，c.）血管生成抑制素，最近发现的内源性抑制剂， 血管生成，主要基于我们实验室的工作。 的 因此，本建议的具体目标是：一。执行第二阶段 用沙利度胺和β-环糊精联合抗血管生成抑制的试验 复发性高级别胶质瘤患者的干扰素;和2.）执行 血管生成抑制素（一种新型抗血管生成抑制剂）的I期试验， 复发性高级别胶质瘤患者。 通过这些例子，我们希望 展示我们在临床前开发和临床方面的经验， 在原发性恶性神经胶质瘤中评价的新药物的试验设计， 以及我们开展相关实验室研究的能力， 最终产生有用的生物学和临床终点。

DESCRIPTION: The overall objective of this UOI application is to provide support for consortia of institutions to perform Phase I and 11 clinical trials of new chemotherapeutic/biologic agents in patients with primary central nervous system (CNS) tumors and to perform ancillary laboratory studies with potential clinical implications. The Harvard/Longwood Brain Tumor Center Trials Group at the Dana-Farber Cancer Institute, Brigham and Women's Hospital, The Children's Hospital, and the Beth Israel Hospital has a large and expanding patient population and commitment to clinical and laboratory research of primary brain tumors. As part of the "North American Brain Tumor Consortium" our general goals will be to perform Phase I and II trials of novel cytotoxic and biologic agents, with a special interest in anti-angiogenic agents. Although San Antonio will function as the pharmacologic center for our consortium, our center is in a position to either pilot experimental and/or extensive single institution pharmacologic/pharmacodynamic studies given our large experience in pharmacology-based Phase I trials. Since the specific agents to be studied over the next four years are unknown at this time, we have chosen to develop protocols that build on our previous work in the pre-clinical and clinical development of three agents with anti-angiogenic activity based on our long-standing interest in tumor-associated angiogenesis: a.) Thalidomide, a teratogenic sedative with anti-angiogenic activity, for which we are just completed a promising Phase 11 trial in patients with malignant gliomas: b.) A new human beta interferon with anti-angiogenic activity and significant antiglioma activity demonstrated in our recently completed Phase I trial; and, c.) Angiostatin, a recently discovered endogenous inhibitor of angiogenesis, based on work done principally in our laboratories. The specific aims of this proposal are therefore; I.) To perform a Phase II trial of combination anti-angiogenesis inhibition with thalidornide and beta interferon in patients with recurrent high grade gliomas; and 2.) To perform a Phase I trial of angiostatin, a novel inhibitor of anti-angiogenesis, in patients with recurrent high grade gliomas. Through these examples, we hope to demonstrate our experience in the preclinical development and clinical trial design of novel agents to be evaluated in primary malignant gliomas, and our capability to develop correlative laboratory studies that may ultimately yield useful biologic and clinical endpoints.