Neurofibromatosis Clinical Consortium Award

Principal Investigator: KORF, BRUCE R
Program: NFRP
Proposal Number: NF110052
Award Number: W81XWH-12-1-0155
Funding Mechanism: Clinical Consortium Award
Partnering Awards:
Award Amount: $9,000,000.00


The Neurofibromatosis Clinical Trials Consortium (NFCTC) has been funded by the Congressionally Directed Medical Research Programs since 2007, with the primary goal of developing and implementing clinical trials to test the effectiveness of new treatments for patients with neurofibromatosis. Advances in the understanding of how the various complications of NF1, NF2, and schwannomatosis come about are increasingly making it possible to develop new drugs or identify existing drugs that may be helpful in treating these complications. Establishing the utility of such treatments, however, requires conducting very careful tests to determine both that the treatments are effective and that they do not cause side effects that limit their use. No single NF clinic is able to conduct trials that are large enough to establish the effectiveness of new treatments, and conducting collaborative trials involving multiple sites raises major ethical and regulatory complexities that can prevent trials from going forward. The NFCTC was established to overcome these barriers. The Consortium consists of an Operations Center at the University of Alabama at Birmingham and, currently, nine patient recruitment sites. The Operations Center provides central coordination of all aspects of the clinical trials, insuring compliance with all regulatory and ethical requirements and managing analysis and collection of all data required to determine the effectiveness of the trial. The nine patient recruitment sites have expertise in management of patients with NF and are collectively able to recruit a large enough number of participants in clinical trials to insure meaningful results. Using this infrastructure, the NFCTC has developed four clinical trials. The existing trials all address NF1, which was decided prior to the establishment of the Consortium in order to focus the effort and improve the chances that the Consortium would be successful in establishing a clinical trials infrastructure. The existing trials address plexiform neurofibromas, learning disabilities, brain tumors, and malignant soft tissue tumors. The successful development of these trials has shown that the Consortium can coordinate large and carefully designed multicenter trials. It has also demonstrated an ability to work with scientists throughout the NF community and to partner with the pharmaceutical industry in making new drugs available. With this background, the NFCTC is now poised to expand its efforts to embrace all forms of neurofibromatosis, i.e., NF1, NF2, and schwannomatosis. Four new clinical trial recruitment sites have been added to the Consortium, and four sites have also established partnerships with nearby institutions. These additions greatly increase the geographical balance of the Consortium and improve the ability to recruit adults with all forms of NF, especially NF2 and schwannomatosis. A new all-electronic data entry system is now in place to collect information in support of clinical trials. The NFCTC includes committees that monitor progress in identification of potential therapies, and these committees have developed multiple clinical trial proposals. Four have been selected by the Steering Committee to submit to an External Review Committee for consideration to launch as the next NFCTC trials. The first of these will focus on hearing nerve tumors in patients with NF2, following up on encouraging early data on the effectiveness of a drug called bevacizumab (Avastin); the second trial will test the medication imatinib mesylate (Gleevec) for treatment of plexiform neurofibromas of the head and neck or pelvis in patients with NF1. This, too, follows up on encouraging data from preliminary testing. Two additional trials, one focusing on fractures of the shinbone that occur in NF1 patients and the other on learning disabilities in NF1 patients, have been proposed for external review; these would be launched in years 2 and 3 of the Consortium if adequate funding is available. Multiple other trials have been proposed by the various disease committees, including trials for NF2 and schwannomatosis. These will be pursued by the Consortium as additional funding sources are identified. The Consortium has had success in partnering with the pharmaceutical industry, as well as private donors and the Children's Tumor Foundation, and is working to achieve financial self-sufficiency. In summary, the NFCTC has established an effective system and collaboration among leading clinical sites to test new therapies for patients with NF. The NFCTC is now poised to expand its efforts on behalf of patients with all forms of neurofibromatosis, providing a critical component of the pipeline by which research advances can be advanced rapidly, safely, and effectively from the laboratory to the clinic to benefit the entire NF community.