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Special Approaches Needed for NF1 Clinical Trials in Children

By October 28, 2009December 18th, 2023Awareness, NF1, Science & Research

It is exciting that we are now in the age of NF1 clinical trials, with a goal to identify drug treatments that can be given safely to both adults and children with NF1. However special considerations are required when figuring out how drugs can be given safely and effectively to children, and as a result, some NF1 clinical trials are being designed specifically for children. This topic is addressed in this month’s Neurology* by a group from the National Cancer Institute headed by Dr. Brigitte Widemann, a renowned leader and pioneer in the field of designing NF1 drug trials.

Looking back a few years, the earliest trials that included children with NF1 (focused on plexiform tumors, and testing chemotherapy agents as well as early candidate drugs such as tipifarnib and pirfenidone) also included children with cancer. However as our knowledge of NF1 tumor biology and clinical management has expanded, pediatric trials have evolved to be NF1-specific. This is a critical breakthrough: there are very important differences between the largely benign tumors seen in NF1, and malignant cancer related tumors. Though NF1 tumors can be debilitating and life threatening, children with NF1 will typically survive much longer than those with cancer; and because plexiform tumors grow (and may respond to drug) slowly, trials – and future prescribed drug treatment regimes – need to be over a longer course of time than when treating cancer, and to give lower doses of drug. Also, different outcome measures may be needed for NF1 trials, including assurance that drug does not have any long-term toxic effects or interfere with the child’s normal growth and development. And in terms of monitoring whether or not the drug is effective, plexiform tumors for example are often lobular and complex, and can be difficult to measure. As a result three-dimensional imaging of plexiform tumor growth (a technology whose use in NF1 tumors was in part pioneered by Dr. Gordon Harris at MGH, with grant funding from the Children’s Tumor Foundation) has been implemented as a standard practice in NF1 pediatric trials so that tumor growth – or shrinkage – can be adequately monitored.

With a few NF1 clinical trials now enrolling children for tumor treatment studies  – including a sorafenib trial funded by the Children’s Tumor Foundation and headed by Dr. Widemann and Dr. Bruce Korf (University of Alabama at Birmingham) – as well as for NF1 learning disabilities treatment studies, its certain our knowledge of this area will expand in the near future.

* Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas. Kim A, Gillespie A, Dombi E, Goodwin A, Goodspeed W, Fox E, Balis FM, Widemann BC. Neurology. 2009 Oct 20;73(16):1273-9