How the North American Brain Tumor Consortium Shaped Clinical Research in Neuro-oncology

US Neurology, 2008;4(2):40-42 DOI: http://doi.org/10.17925/USN.2008.04.02.40
Citation US Neurology, 2008;4(2):40-42 DOI: http://doi.org/10.17925/USN.2008.04.02.40

The North American Brain Tumor Consortium (NABTC) is one of three multi-institutional consortia initially funded by the National Cancer Institute (NCI) in 1994 with the primary purpose of efficiently evaluating novel treatments in adults with central nervous system (CNS) tumors. Its current counterpart is New Approaches to Brain Tumor Therapy (NABTT) and although the consortia share common goals, they have thus far had separate identities and infrastructures. As a new era begins in which these two consortia will merge to form the Adult Brain Tumor Consortium (ABTC), it is important to reflect on and learn from past successes and failures. Therefore, I am happy to have been asked to write this editorial describing the lessons learned at the NABTC and how the organization has influenced neuro-oncology clinical research.

The NCI’s decision to prioritize early clinical trials in this orphan disease was a critical step in forming the consortia. The recognition of the significant morbidity and high mortality associated with CNS tumors, despite the relatively low incidence compared with other solid tumors, and the dedication of basic science and clinical researchers to improving the outcome of patients were important factors in the success of the consortia. By 1994, the field of neuro-oncology had grown enough to sustain the clinical research effort proposed by the NCI. Prior to this effort, most therapeutic agents were inherited from phase I experience in solid cancers and subsequently tested in neuro-oncology patients. One reason for this was the reluctance of pharmaceutical companies to invest in early clinical development of their product in such a small-volume disease. There were also concerns that agents would not be safely tolerated by patients with a CNS disease that carried such a poor prognosis. A major advantage of forming the NABTC was that it established the credibility needed to generate funding for research and to gain access to new agents for early testing in brain tumor patients. One important objective of the consortia, therefore, was to demonstrate the ability to complete well-designed and -conducted multi-institutional phase I/II trials in this challenging patient population. Bolstered by public awareness regarding the need for clinical research devoted to brain tumors and an increase in patient advocacy groups, a significant effort began to better understand the disease and find effective therapies.

Under the leadership of Michael Prados, MD, the NABTC invited 10 institutions to participate in the consortium. All principal investigators (PIs) and representatives from each site met twice a year to review the progress of the consortium with respect to patient accrual, data management and regulatory compliance, and proposals for new protocols, and to discuss priorities for the group. Monthly conference calls also facilitated communication among the members and were critical for discussion of toxicity assessments and plans for dose escalation in phase I studies.

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