The broad, long-term objective of this application is to improve the effectiveness of management strategies for patients with malignant glioma, a disease process that results in >10,000 deaths annually in the U.S. Standard therapeutic approaches with surgery, external beam radiotherapy and chemotherapy have resulted in minimal survival gain and the lethality approaches 100%, with average survival ranging from 9 to 18 months, depending on various prognostic factors. The specific focus of this grant will be to continue previously initiated clinical trials, design and implement new strategies and carefully analyze data generated from a series of investigational Phase I/II trials in adult patients with malignant glioma. In order to realize meaningful results expeditiously, the investigational studies will be performed simultaneously at several institutions which constitute the North American Brain Tumor Consortium (NABTC). We intend to perform 6 to 8 trials annually, enrolling between 80 to 140 fully evaluable cases per year through the consortium. All patients will be evaluated and treated by a multidisciplinary team composed of neurosurgeons, oncologists, radiation oncologists, neuro-pathologists, neuroradiologists and clinical research nurses, with the data collected prospectively and monitored and evaluated by dedicated data managers and statisticians. In addition to this intense multidisciplinary clinical effort, the consortium arrangement will permit networking of ideas to allow creative cooperation and maintain the highest level of interest in translational laboratory-based clinical research. The NABTC agreement provides a rich resource of multiple tissue-banks and pharmacokinetic samples for sharing of tissue and serum specimens for ancillary laboratory-based studies and subsequent clinical correlations. Such correlations may include new developments in drug and radiation resistance, radiation sensitization, induction of apoptosis, signal transduction modulation, improvements in therapeutic radiation delivery techniques, better drug sequencing, superior understanding of chemotherapeutic metabolism under altered hepatic enzymologic conditions induced by steroids and anticonvulsants, incorporation of gene therapy in future trials, etc. The entire effort will be intimately linked with the ongoing interests, needs and support of the Cancer Therapy Evaluation Program and the Radiation Research Program of the Division of Cancer Treatment Diagnosis and Centers at the National Cancer Institute. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA062421-12
Application #
7007281
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O2))
Program Officer
Wu, Roy S
Project Start
1994-04-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
12
Fiscal Year
2006
Total Cost
$122,142
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Vivanco, Igor; Robins, H Ian; Rohle, Daniel et al. (2012) Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Discov 2:458-71
Iwamoto, Fabio M; Lamborn, Kathleen R; Robins, H Ian et al. (2010) Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro Oncol 12:855-61
Raizer, Jeffrey J; Abrey, Lauren E; Lassman, Andrew B et al. (2010) A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas. Neuro Oncol 12:87-94
Hendrickson, Ronald C; Cicinnati, Vito R; Albers, Andreas et al. (2010) Identification of a 17beta-hydroxysteroid dehydrogenase type 12 pseudogene as the source of a highly restricted BALB/c Meth A tumor rejection peptide. Cancer Immunol Immunother 59:113-24
Norden, Andrew D; Raizer, Jeffrey J; Abrey, Lauren E et al. (2010) Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol 96:211-7
Raizer, Jeffrey J; Abrey, Lauren E; Lassman, Andrew B et al. (2010) A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. Neuro Oncol 12:95-103
Butowski, Nicholas; Lamborn, Kathleen R; Lee, Bee L et al. (2009) A North American brain tumor consortium phase II study of poly-ICLC for adult patients with recurrent anaplastic gliomas. J Neurooncol 91:183-9
Wen, Patrick Y; Yung, W K Alfred; Lamborn, Kathleen R et al. (2009) Phase II study of imatinib mesylate for recurrent meningiomas (North American Brain Tumor Consortium study 01-08). Neuro Oncol 11:853-60
Guo, Deliang; Prins, Robert M; Dang, Julie et al. (2009) EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy. Sci Signal 2:ra82
Chang, Susan M; Lamborn, Kathleen R; Kuhn, John G et al. (2008) Neurooncology clinical trial design for targeted therapies: lessons learned from the North American Brain Tumor Consortium. Neuro Oncol 10:631-42

Showing the most recent 10 out of 24 publications