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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项硼替佐米和替莫唑胺用于复发性原发性脑肿瘤（包括原发性中枢神经系统淋巴瘤）或复发性脑转移或确诊的转移性或不可切除的实体瘤的I期研究，标准治疗或姑息措施不存在或不再有效。本研究的目的是：1.1确定硼替佐米和替莫唑胺联合治疗复发性高级别胶质瘤、复发性转移性脑瘤或其他难治性实体瘤患者的剂量限制毒性（dlt）和最大耐受剂量（MTDs）。1.2评价硼替佐米在服用肝酶诱导抗惊厥药物患者（A组）和未服用抗惊厥药物患者（B组）中的药代动力学。1.3通过测定脑脊液中硼替佐米的药物水平来评估硼替佐米是否会进入中枢神经系统。1.4描述用硼替佐米和替莫唑胺治疗获得完全缓解或部分缓解的患者比例。

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.