A PHASE I STUDY OF BORTEZOMIB AND TEMOZOLOMIDE IN PATIENTS WITH REFRACTORY SOLID

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项针对复发性原发脑瘤(包括原发中枢神经系统淋巴瘤)、复发性脑转移或确诊为转移性或无法切除的实体肿瘤的患者进行的硼替佐米和替莫唑胺的I期研究，这些患者的标准治疗或姑息措施尚不存在或不再有效。本研究的目的是：1.1确定复发性高级别胶质瘤、复发性脑转移瘤或其他难治性实体瘤患者联合应用博替佐米和替莫唑胺的剂量限制毒性(DLTS)和最大耐受量(MTDS)。1.2评价硼替佐米在服用肝酶诱导性抗惊厥药的患者(A组)和未服用该药的患者(B组)中的药代动力学。1.3通过测量脑脊液中的药物浓度来评估Bortezomib是否进入中枢神经系统。1.4描述接受波替佐米和替莫唑胺治疗的研究患者中得到确认的完全缓解或部分缓解的比例。

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. This is a Phase I study of bortezomib and temozolomide in subjects with a recurrent primary brain tumor (including primary CNS lymphoma) or recurrent brain metastases or confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective. The objectives of this study are: 1.1 To determine the dose-limiting toxicities (DLTs) and maximum tolerated doses (MTDs) for the combination of bortezomib and temozolomide in patients with recurrent high-grade gliomas, recurrent metastatic brain tumors or other refractory solid tumors. 1.2 To evaluate the pharmacokinetics of bortezomib in patients taking hepatic enzyme-inducing anticonvulsants (Group A) and in those who are not (Group B). 1.3 To assess whether bortezomib crosses into the central nervous system by measuring drug levels in the cerebrospinal fluid. 1.4 To describe the proportion of study patients treated with bortezomib and temozolomide who obtain a confirmed complete response or partial response.