THERAPEUTICS STUDIES OF PRIMARY CNS MALIGNANCIES

说明： 此UOI应用程序的总体目标是为 由机构组成的财团将进行新药物的第一期及第十一期临床试验 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/朗伍德脑瘤中心 达纳-法伯癌症研究所的试验小组，布里格姆和妇女 医院，儿童医院和贝丝以色列医院有一个很大的 以及扩大患者数量和对临床和实验室的承诺 原发脑肿瘤的研究。作为“北美大脑”的一部分 我们的总体目标将是进行I期和II期试验 新的细胞毒性和生物制剂，特别对 抗血管生成药物。尽管圣安东尼奥将作为 作为我们联盟的药理中心，我们的中心有能力 试点、试验性和/或广泛的单一机构 药理/药效学研究给了我们在 以药理学为基础的I期试验。由于需要研究的具体试剂 在未来四年是未知的时候，我们已经选择了发展 方案建立在我们之前在临床前和临床上的工作基础上 基于OUR的三种抗血管生成药物的研究进展 对肿瘤相关血管生成的长期兴趣：a.)沙利度胺 具有抗血管生成活性的致畸镇静剂，我们只是 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干扰素和 在我们最近完成的阶段显示了显著的抗胶质瘤活性 我试行；以及，c.)血管抑素，一种新近发现的内源性血管生成抑制物 血管生成，主要基于我们实验室所做的工作。这个 因此，这项建议的具体目标是：执行阶段II的步骤 沙利度胺和β-受体拮抗剂联合抗血管生成作用的实验研究 对复发的高级别胶质瘤患者使用干扰素；表演，表演 一种新的抗血管生成抑制剂Angiostatin的I期试验 复发的高级别胶质瘤患者。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 用于评估原发恶性胶质瘤的新药物的试验设计， 以及我们开发相关实验室研究的能力 最终产生有用的生物和临床终点。

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.