NABTT-New Approaches to Brain Tumor Therapy (CNSC)

描述（由申请人提供）：麻省总医院是NABTT协议的共同创始机构和第三大收益来源。为了支持I期和II期研究，我们获得了机构和私人的财政支持，提供了应计基础设施的质量控制、少数群体应计、患者倡导、数据制表、AE报告和内部审计。MGH的研究人员在NABTT基因治疗、教育和非胶质瘤协议委员会中担任主席职务，并担任P.l。在包括CPT-11、高剂量MTX/Thiot-tepa、Onyx 0-15和奥沙利铂等方案的研究中，他曾参与撰写了关于cpt -450诱导、苏拉明和基因治疗的开创性NABTT报告。MGH资助的PO-1（脑肿瘤基因治疗）提供了试点NABTT试验，涉及的载体包括腺β - Ifn、疱疹、腺-tk和疱疹-环磷酰胺以及CPT-11方案。对于这些NABTT研究来说，最重要的是我们的啮齿动物试验、灵长类动物安全性研究和IND应用模板。(2)提供NABTT药代动力学CORE，提供i期研究设计和药物pK分析（Supko博士），以及Glivec在CRT， ST1481， SrcNu和新型端粒酶细胞因子系统后的中试试验。此外，我们还为实时测定人体肿瘤内活性药物的新型微透析技术提供了基础。第一种药物可能是EMD，一种新型整合素抑制剂。(3)磁共振血流量、容量和通透性的放射学CORE研究（Hunter博士和WORLDCARE）对血管生成抑制剂的未来试验至关重要。我们将向NABTT提供CORE设备，在HPPA规定的范围内，在单一平台上进行成像。这些放射学工具提供肿瘤的血管代谢图，与VEGf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(dr。路易斯和巴切勒)。通过提供Frye-Halloran遗赠，我们服务于NABTT教育功能。两个专题讨论会（神经肿瘤学中的微透析导管技术）（血管生成成像）和两个计划中的专题讨论会（溶瘤性疱疹载体- 2003年9月和脑淋巴瘤新策略- 2003年12月）已经或将为NABTT试验的实施提供范式转变。

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.