The neurofibromatoses (NF)--including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis--are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF.
AimThe goal of the group’s efforts is to recommend outcome measures and methodologies that will be used by REiNS members and by other researchers to standardize endpoints for NF clinical trials.
ContributorsPlotkin, Scott R. Blakeley, Jaishri O. Dombi, Eva Fisher, Michael J. Hanemann, C. Oliver Walsh, Karin S. Wolters, Pamela L. Widemann, Brigitte C.
Disease Category: Genetic disorders
Disease Name: Neurofibromatoses
Age Range: 0 - 100
Sex: Either
Nature of Intervention: Any
- None
- Systematic review of outcomes measured in trials
- Literature review
- Semi structured discussion
- Teleconferences
The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children’s Tumor Foundation meeting to achieve consensus within the NF community about future clinical trials and to accelerate the identification of agents that will benefit individuals with NF. The REiNS Collaboration is organized around 7 working groups, with leaders of the groups identified based on their expertise at the initial meeting in 2011. Each REiNS group establishes a meeting schedule; the majority of meetings are held by teleconference. In-person meetings of the entire group are held at least twice per year to coordinate efforts among the working groups and to achieve consensus for recommendations. The leadership team held a preliminary meeting with the US Food and Drug Administration (FDA) to discuss endpoints for NF trials. At this meeting, the FDA encouraged the REiNS Collaboration to use validated functional and patient-reported outcomes for trials intended for drug approval. The authors provided a summary of published clinical trials for Neurofibromatosis.