NABTT2111 - BMS-247550

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本临床试验的剂量探索（持续重新评估方法（CRM））阶段的目的是1）确定复发性恶性胶质瘤成人患者接受（A组）或未接受（B组）已知由P450肝酶复合物代谢的抗惊厥药给药时BMS-247550的最大耐受剂量。2)描述该给药途径的药代动力学，测量BMS-247550，并确定肝酶诱导药物（如抗惊厥药）对药代动力学的影响。最大耐受剂量（MTD）阶段的安全性/疗效的目的是1）确定复发性胶质瘤成人患者对MTD BMS-247550给药的缓解率。2)描述该方案在复发性恶性胶质瘤成人患者中的毒性。次要目的a）确定复发性恶性胶质瘤成人患者中6个月无进展生存期的患者百分比、无进展生存期的持续时间以及与该治疗相关的生存期。BMS-247550是Bristol-Myers Squibb生产的天然产物埃坡霉素B的甲基半合成类似物。在乳腺癌和宫颈癌患者中观察到了客观反应; 12名晚期卵巢癌患者中有2名CA 125降低> 50%（所有乳腺癌、宫颈癌和卵巢癌患者既往均接受过紫杉烷治疗）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objectives of the Dose Finding (Continual Reassessment Method (CRM)) phase of this clinical trial are 1) To determine the maximum tolerated dose of BMS-247550 when administered to adults with recurrent malignant gliomas, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex. 2) To describe the pharmacokinetics of this route of administration, measuring BMS-247550, and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants , on the pharmacokinetics . The objectives for the Safety/Efficacy at Maximum Tolerated Dose (MTD) phase are 1) To determine the response rate of adult patients with recurrent glioma to BMS-247550 administered at the MTD. 2) To describe the toxicity associated with this regimen in adult patients with recurrent malignant gliomas. Secondary Objective a) To determine the percent of patients with 6 month progression free survival, duration of progression free survival and survival associated with this therapy in adult patients with recurrent malignant gliomas. BMS-247550 is a methyl, semi-synthetic analog of the natural product epothilone B produced by Bristol-Myers Squibb. Objective responses have been observed in patients with breast and cervical cancer; with > 50% reduction in CA125 in two of 12 patients with advanced ovarian cancer (all breast, cervical and ovary cancer patients had prior taxane therapy).