A Framework for Prioritizing Novel Agents in Malignant Peripheral Nerve Sheath Tumor Trials: A report from the Neurofibromatosis Clinical Trials Consortium

Abstract

Malignant peripheral nerve sheath tumors (MPNST) are soft tissue sarcomas, occurring either in people with Neurofibromatosis Type 1 (NF1) or sporadically, with a tendency for recurrence and distant metastases, and poor survival rates. The only proven curative treatment is complete oncologic resection, and there is currently no FDA-approved drug for the treatment of MPNST. Multiple clinical trials have failed to achieve improvement in survival and novel therapeutic approaches are urgently needed. To address this need, members of the MPNST Committee of the Congressionally Directed Medical Research Programs-supported Neurofibromatosis Clinical Trials Consortium convened to develop a framework to prioritize therapeutic agents with the highest potential for successful clinical development. We review the potential agents that may be prioritized and propose a methodology to evaluate available preclinical and clinical data. Increasing the availability and use of diverse preclinical models and defining the best preclinical endpoints prior to clinical translation can increase the success of clinical trials. Subsequently, utilizing a platform trial design can accelerate the clinical development process and facilitate patient accrual. It is imperative to foster collaborations with pharmaceutical companies and community partners. The integration of preclinical and clinical evaluation in an iterative and informative process can accelerate effective clinical development.