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. ? ? ?
