NABTT-New Approaches to Brain Tumor Therapy (CNSC)

描述(由申请人提供)：马萨诸塞州综合医院是NABTT方案的共同创始机构和第三个主要收益来源。为了支持第一阶段和第二阶段的研究，我们获得了机构和私人财政支持，提供了应计基础设施、少数人应计、患者倡导、数据制表、AE报告和内部审计的质量控制。MGH研究员在NABTT基因治疗、教育和非胶质瘤方案委员会担任主席职务，担任CPT-11、大剂量甲氨蝶呤/硫代Tepa、玛瑙0-15和奥沙利铂等方案的P.L.S，并共同撰写关于CYP-450诱导、苏拉明和基因治疗的NABTT开创性报告。MGH资助的PO-1(脑肿瘤的基因治疗)提供了NABTT试点试验，涉及的载体包括腺-β干扰素、疱疹病毒、腺病毒-tk和疱疹-环磷酰胺和CPT-11协议。对于这些NABTT研究来说，最重要的是我们用于啮齿动物测试、灵长类动物安全性研究和IND应用的模板。(2)提供NABTT药代动力学核心，该核心提供第1阶段研究设计和药物PK分析(Supko博士)，以及在CRT、ST1481、SrcNu和一个新的端粒酶-细胞因子系统之后Glivec的初步试验。此外，我们还为实时检测人体肿瘤内活性药物的新型微透析技术提供了基础。第一种药物很可能是EMD，一种新型的整合素抑制剂。(3)对MR血流量、血容量和渗透性的放射核心研究(亨特博士和Worldcare)将是未来血管生成抑制剂试验的关键。我们将为NABTT提供核心设施，以便在HPPA法规范围内的单一平台内进行成像。这些放射成像工具提供了肿瘤的血管代谢图，与血管内皮生长因子和循环内皮细胞的分析相关。我们将与NABTT的同事合作，提供新的神经病理分层标准(Louis和Batchelor博士)。通过提供Frye-Halloran遗赠，我们服务于NABTT教育职能。两个研讨会(神经肿瘤学中的微透析导管技术)(血管生成成像)和两个计划中的研讨会(溶瘤疱疹病毒载体-2003年9月和脑淋巴瘤新策略-2003年12月)已经或将在NABTT试验的进行中提供范式转变。

DESCRIPTION (provided by applicant): The Massachusetts General Hospital is co-founding institution and the third major source of accrual to NABTT protocols. To support phase I and II studies we have obtained both institutional and private financial support which provides for quality control of accrual infrastructure, minority accrual, patient advocacy, data tabulation, AE reporting and internal audits. The MGH investigators perform Chair functions on NABTT committees for Gene Therapy, Education and non-Glioma Protocols and serve as P.l.'s for protocols including CPT-11, High Dose MTX/Thiot-tepa, Onyx 0-15 and oxaliplatin and have co-authored seminal NABTT reports of CYP-450 induction, Suramin, and gene therapy. The MGH funded PO-1 (Gene Therapy of Brain Tumors) provides for pilot NABTT trials involving vectors which include Adeno-Beta Ifn, herpes, Adeno-tk and Herpes-Cytoxan and CPT-11 protcols. Most important for these NABTT studies is our template for rodent testing, primate-safety studies and IND application. (2) Provision of the NABTT Pharmacokinetic CORE which provides Phase 1 study design and drug pK analysis (Dr. Supko) as well as pilot trials of Glivec after CRT, ST1481, SrcNu and a novel telomerase-cytokine system. In addition we provide the basis for novel microdialysis techniques for real-time determination of activated drug within human tumors. The first drug is likely to be EMD, a novel integrin inhibitor. (3) Radiographic CORE studies (Dr. Hunter and WORLDCARE) of MR blood flow, volume and permeability will be crucial to future trials of angiogenesis inhibitors. We will provide CORE facilities to NABTT for imaging within a single platform within the confines of HPPA regulations. These radiographic tools provide vascular-metabolic maps of tumor which are correlated with analyses of VEGf and circulating endothelial cells. We will work with NABTT colleagues to provide novel neuropathologic stratification criteria (Drs. Louis and Batchelor). Through the provision of the Frye-Halloran bequest, we serve the NABTT Educational function. Two symposia (Microdialysis Catheter techniques in Neuro-oncology)(Imaging of Angiogenesis) and two planned symposia (Oncolytic herpes vectors -September 2003 and Brain Lymphoma Novel Strategies - December 2003) have or will provide paradigm-shifts in the conduct of NABTT trials.