The Massachusetts General Hospital is a co-founding institution of and major contributor to the consortium New Approaches to Brain Tumor Therapy (NABTT). The MGH role has been highly productive with patient accrual second only to the NABTT center. In this application we provide for quality control of these clinical trials as well as internal audits through our protocol office. The MGH investigators perform Chair functions on three NABTT committees (Gene Therapy, Morbidity and Corporate), have sponsored two active protocols (9-AC Recurrent and High Dose MTX Therapy of Brain Lymphoma with Deferred Radiotherapy), co- authored the seminal NABTT data relating drug levels to CYP-450 induction, and established the Corporate-NABTT interaction. The MGH funded PO-1 (Gene Therapy of Brain Tumors) reflects translational clinical studies which flourished from NABTT interactions with Drs. Grossman and Colvin. The molecular classification system of Dr. D. Louis (MGH), which will serve to provide new stratifications for NABTT studies, reflects the utility of the NABTT Brain Tumor Bank. The MGH provides three resources to NABTT: (1) Genetic therapies (Drs. Breakefield and Chiocca), (2) Phase I agents (Dr. Chabner) their analysis and modeling (Dr. Supko), and (3) Assessment of morbidity and quality of life (Drs. Batchelor and Barker). (1) Dr. Hochberg heads the NABTT gene therapy committee which will provide the NABTT protocols for p53 transfection (Onyx, Introgen, Schering) to commence in 1997-8. We will make available to collaborators our herpes, adeno and amplicon vectors expressing CYP450 for the activation of prodrugs within gliomas. Most important for these NABTT studies is our template for rodent testing, primate-safety and IND application. We serve as a resource to NABTT for assessment of neuropathologic endpoints, evaluation of transgene expression and efficacy testing. (2) Dr. Chabner heads the phase I drug committee for NABTT and will make available a variety of agents including sarCNU, spicamycin and angiogenesis inhibitors. These latter compounds include TNP-470, penicillamine and VEGF MAB. TNP-470 is under evaluation at the MGH using of fMRI and fCT as surrogate markers of glioma angiogenesis. These techniques can be co-registered over FDG-PET images to provide vascular-metabolic maps of tumor, area- around-tumor and normal brain tissue. These maps will be correlated with in vitro analysis of vascular markers performed by our collaborator Dr. S. Brem. (3) Dr. Hochberg brings to NABTT the pilot study of an industry-sponsored assessment of quality of life of American patients with malignant glioma. This study will provide for validation of both physician and patient instruments for assessing outcome. The instruments are viewed as potential replacement for the KPS.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01CA062406-05
Application #
2469550
Study Section
Special Emphasis Panel (ZCA1-CRB-K (O1))
Program Officer
Krosnick, Steven H
Project Start
1994-03-18
Project End
2002-12-31
Budget Start
1998-03-01
Budget End
1998-12-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Phuphanich, Surasak; Carson, Kathryn A; Grossman, Stuart A et al. (2008) Phase I safety study of escalating doses of atrasentan in adults with recurrent malignant glioma. Neuro Oncol 10:617-23
Grossman, Stuart A; Carson, Kathryn A; Batchelor, Tracy T et al. (2006) The effect of enzyme-inducing antiseizure drugs on the pharmacokinetics and tolerability of procarbazine hydrochloride. Clin Cancer Res 12:5174-81
He, X; Batchelor, T T; Grossman, S et al. (2004) Determination of procarbazine in human plasma by liquid chromatography with electrospray ionization mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 799:281-91
Gilbert, Mark R; Supko, Jeffrey G; Batchelor, Tracy et al. (2003) Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma. Clin Cancer Res 9:2940-9
Grossman, S A; Hochberg, F; Fisher, J et al. (1998) Increased 9-aminocamptothecin dose requirements in patients on anticonvulsants. NABTT CNS Consortium. The New Approaches to Brain Tumor Therapy. Cancer Chemother Pharmacol 42:118-26
Fetell, M R; Grossman, S A; Fisher, J D et al. (1997) Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium. J Clin Oncol 15:3121-8