Early-Phase Trial Shows Shrinkage in Pediatric Neural Tumors

In an early phase clinical trial of a new oral drug, selumetinib, children with the common genetic disorder neurofibromatosis type 1 (NF1) and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage. NF1 affects 1 in 3,000 people. Study results appeared Dec. 29 in the New England Journal of Medicine.

The multicenter phase I clinical trial, which included 24 patients, was led by Dr. Brigitte Widemann of NCI’s Pediatric Oncology Branch, and was sponsored by NCI’s Cancer Therapy Evaluation Program. 

The study, conducted at the Clinical Center and three participating sites, took advantage of techniques developed by Widemann’s team that enabled precise measurement of the plexiform neurofibromas. Experiments in mice that developed neurofibromas due to genetic modifications were performed at Cincinnati Children’s Hospital in the laboratory of Dr. Nancy Ratner. 

Plexiform neurofibromas develop in up to 50 percent of people with NF1. The majority of these tumors, which can cause significant pain, disability and disfigurement, are diagnosed in early childhood and grow most rapidly prior to adolescence. Complete surgical removal of the tumors is rarely feasible; incompletely resected tumors tend to grow back.

The primary aim of the clinical trial was to evaluate the toxicity and safety of selumetinib in patients with NF1 and inoperable plexiform neurofibromas, and, encouragingly, most of the selumetinib-related toxic effects were mild.