The group of disorders collectively called “neurofibromatoses” (NF) includes three distinct conditions: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). Decades of research into these disorders have led to insights into possible new approaches to treatments using medications that target the underlying disease mechanisms. Determining whether these treatments are effective, however, requires conducting carefully designed and executed clinical trials with well-defined outcome measures. Major obstacles to conducting such trials include the difficulty in recruiting a sufficient number of participants to obtain a statistically meaningful measure of success; the need to pay careful attention to quality control in trial conduct to ensure the accuracy of results and safety of participants; and the complexities of complying with regulatory requirements, including those of institutional review boards to ensure that the safety and rights of participants are respected, as well as requirements of the Food and Drug Administration in the use of experimental drugs. The Neurofibromatosis Clinical Trials Consortium (NFCTC) was established by the Congressionally Directed Medical Research Programs of the Department of Defense to address these issues and accelerate the conduct of reliable clinical trials for all forms of NF.

The NFCTC consists of an Operations Center at the University of Alabama at Birmingham, a Data Coordinating Center at Children’s Hospital of Philadelphia, and 25 participant recruitment sites (including 15 primary sites and 10 affiliate sites). The NFCTC has convened committees to more rapidly identify promising new treatments for multiple complications of NF1, NF2, and SWN; these committees use this information to develop new clinical trials. Since the NFCTC was established in 2006, 15 clinical trials have been launched (with 4 more to be launched in the next 9 months), more than 480 participants have been enrolled, and the NFCTC has worked together with pharmaceutical companies and patient support organizations to leverage more than $5 million in additional funding to support and expand its number of clinical trials.

In this application for continued funding of the NFCTC, we expect to open two trials in the first year and to launch at least 12 additional clinical trials during the 10 years of this funding cycle. We have trials in preparation or consideration for multiple complications of NF1 (including attention deficit disorder, malignant peripheral nerve sheath tumors, brain tumors, plexiform neurofibromas, cutaneous neurofibromas, and bone disorders); NF2 (including hearing nerve tumors and tumors of the membranes that cover the brain and spinal cord [meningiomas]); and SWN (including pain due to tumors or treatment of the tumors themselves). We are also initiating a number of innovations in this proposal for continued funding. Many of our clinical trials have involved treatment of similar complications, such as plexiform neurofibromas, brain tumors, or hearing nerve tumors, with different drugs. We will develop an approach called a “platform trial” that uses the same clinical trial structure for trials involving a specific complication, such as plexiform neurofibroma. This will facilitate more rapid development of clinical trials for common NF complications. We are also developing a registry of all clinical trial participants, which will make it easier to track long term outcomes of clinical trials. A clinical trials group is being developed in Europe, called EU-PEARL; the NFCTC is working with EU-PEARL to ensure that we will be able to compare results across trials conducted in the U.S. and Europe and make it possible to consider collaborative trials across both consortia. A collection of imaging studies (such as MRI scans) for all trial participants will be set up to facilitate further research using this resource, and we will increase our efforts to save samples of tissues obtained during clinical trials for further research. We have been collecting patient-reported outcomes in most of our clinical trials and will be increasing this effort using devices such as iPads and other mobile devices. We will pilot test a program to include patient/family input in the design of clinical trials and increase our efforts to include in our clinical trials participants representing diverse populations in the U.S., especially those who have historically been under-represented in clinical trials.

The NFCTC is committed to continuing to serve the NF community by conducting clinical trials as rapidly and reliably as possible for all forms of neurofibromatosis, always respecting the safety and rights of study participants. There have already been significant successes in development of new treatments for some complications of NF, but much work remains to be done to address the full range of complications of NF1, NF2, and SWN. The NFCTC looks forward to continuing to advance its efforts on behalf of the NF patient community and strengthen its partnerships with that community to ensure that new therapeutic developments can be moved into clinical practice as rapidly and responsibly as possible.