Everolimus Therapy for NF1-Optic Gliomas in Children: A Clinical Trial

Posted January 19, 2021

Nicole Ullrich, M.D., Ph.D., Boston Children’s Hospital

Nicole Ullrich, M.D., Ph.D., Boston Children’s Hospital Dr. Nicole Ullrich

Low-grade gliomas (LGGs) are a common type of brain tumor in children with Neurofibromatosis type 1 (NF1). When LGGs occur along the optic pathway, they can affect visual acuity. The mammalian target of the rapamycin (mTOR) pathway is activated in NF1-associated LGGs and can lead to abnormal cell growth, cell proliferation, and angiogenesis. While previous studies have assessed chemotherapy for NF1-associated LGGs, targeted treatment with mTOR inhibitors has not been extensively studied in the NF1 population. 

Based on preclinical observations, Dr. Nicole Ullrich and her team launched a clinical trial in the Neurofibromatosis Clinical Trials Consortium (NFCTC, fiscal year 2006 [FY06]) studying the efficacy of the oral mTOR inhibitor everolimus in NF1-associated pediatric LGGs and its impact on visual acuity in NF1- associated optic pathway gliomas. Children with radiologic-progressive, NF1-associated LGG and prior treatment with chemotherapy were enrolled to receive daily oral everolimus. The team analyzed whole blood both prior to, during, and after treatment for everolimus levels, as well as markers of PI3K/mTOR pathway inhibition. Serial MRIs were obtained during the course of treatment. The primary endpoint was progression-free survival at 48 weeks. They observed that 68% of participants demonstrated either shrinkage or arrest of tumor growth. Of these, 10/15 remained free of progression, and all remaining participants were alive at completion of therapy. To study the impact of everolimus on visual acuity, Dr. Ullrich and her team collected visual acuity data before and after treatment. They observed that everolimus treatment was able to stabilize (76%) visual acuity in a majority of children with optic pathway glioma, and some children even saw an improvement (16%). 

These two studies demonstrated that everolimus can impact both LGG growth as well as visual acuity related to optic pathway gliomas. Specifically, patients with recurrent/progressive NF1-associated LGGs demonstrated tumor stability/shrinkage during everolimus treatment with a well-tolerated toxicity profile. Importantly, this treatment was associated with functional stabilization and/or improvement of visual acuity in children with optic pathway gliomas. Taken together, these findings indicate everolimus as an effective agent in this patient population. 

The NFCTC was established through FY05 Neurofibromatosis Research Program (NFRP) funding to develop and perform Phase I and II clinical trials for the management and treatment of NF complications in children and adults. Over the years, the NFCTC has expanded from 9 to 15 primary sites with an additional 10 affiliate sites. The Operations Center is housed at the University of Alabama at Birmingham under the direction of Dr. Bruce Korf, and the NFCTC Steering Committee is led by Dr. Michael Fisher at the Children’s Hospital of Philadelphia/ University of Pennsylvania. Since the development awards offered in FY05, the NFCTC has been supported by additional awards from the NFRP in FY06, FY11, and FY16.

Nicole Ullrich, M.D., Ph.D., Boston Children’s Hospital Dr. Ullrich and team


Public and Technical Abstract: Neurofibromatosis Consortium

Top of Page

Last updated Thursday, May 26, 2022