Consensus for NF clinical trials

Abstract

The neurofibromatoses (NFs) can result in substantial morbidity in affected patients. In order to accelerate the development of effective therapies for NF-related tumor and nontumor manifestations, the development of standardized meaningful outcome measures for clinical trials is critical. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for outcome measures and endpoints in future NF trials and provided the first set of recommendations in a Neurology ® supplement in 2013. This second supplement updates on clinical trials that have incorporated the recommended measures and provides new recommendations for (1) standardized and specific cognitive assessment tools for use in NF clinical trials, (2) patient-reported outcome measures including pain and physical functioning, (3) functional outcome measures for airway plexiform neurofibromas, (4) the use of whole-body MRI in NF, and (5) the development of biomarkers in NF and guidelines for collection of biospecimens and establishment of biobanks for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis. Through engagement of the NF research community, regulatory agencies, NF advocacy groups, industry, and patients with NF, REiNS will provide a framework for comprehensive review of these recommendations, continue development of outcome measures relevant to patients, and compare results of trials, which use identical outcome measures. Neurology ® 2016;87 (Suppl 1):S1-S3 GLOSSARY NF 5 neurofibromatosis; NF1 5 neurofibromatosis 1; NF2 5 neurofibromatosis 2; NRS-11 5 Numeric Rating Scale-11; PRO 5 patient-reported outcomes; REiNS 5 Response Evaluation in Neurofibromatosis and Schwannomatosis.The NFs-including NF1, NF2, and schwannomatosis-are genetic tumor-predisposition syndromes characterized by the development of multiple tumor manifestations, in particular nerve sheath tumors, for most of which no standard treatment options other than surgery exist. [1][2][3] In addition, patients with NF can develop multiple nontumor manifestations, affecting many organ systems, which can result in substantial morbidity and reduced quality of life. There is an unmet need for effective medical therapies for NF-related manifestations. Differences between NF-related tumors and nonsyndromic solid cancers have limited the applicability of clinical trial designs used in oncology trials to the development of trials for NF. 4 The REiNS International Collaboration was established in 2011 with the primary goal to achieve consensus within the NF community for outcome measures and endpoints for future NF trials. A description of the REiNS International Collaboration and its 7 working groups and initial recommendations of 4 working groups were published previously in Neurology. 5-10In brief, the imaging working group provided recommendations for the use of MRI with volumetric analysis to evaluate response in clinical trials targeting histologically beni...

Advancing neurofibromatosis and schwannomatosis clinical trial design: Consensus recommendations from the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration

“…Three previous supplements published in Neurology ® in 2013, and 2016, and 2021 set forth a variety of recommendations for clinical trial design, gathered stakeholder perspectives on clinical trials, and generated empirical evidence on the reliability of proposed outcomes. 4 – 6 A summary of all currently recommended measures is available at the REiNS website at https://ccrod.cancer.gov/confluence/display/REINS/Recommendations ; these include the use of volumetric magnetic resonance imaging (MRI) analysis to assess response in clinical trials and the use of various functional and patient-reported outcome measures to evaluate clinical benefit. Many of these measures were incorporated into the SPRINT registration trial, which established the efficacy of selumetinib for treatment of inoperable plexiform neurofibromas in pediatric patients with NF1.…”

Enhancing Neurofibromatosis Clinical Trial Outcome Measures Through Patient Engagement

“…[4][5][6] The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration has played a key role in the creation and dissemination of outcome measures for clinical trials of neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. [7][8][9] Recognizing the potential benefits of patient engagement on this work, REiNS invited patients with neurofibromatosis (NF) and caregivers to join the organization in 2017. In 2019, we administered an online survey of REiNS members to evaluate this patient representative program.…”

Neurofibromatosis Clinical Trials—REiNS Collaboration 2020 Recommendations

“…Since its founding in 2011, the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration has worked to develop standardized, practical, and clinically meaningful outcome measures for clinical trials in these conditions. Two previous supplements published in Neurology ® in 2013 1 and 2016 2 set forth a variety of recommendations that are summarized in the table.…”