Posted February 4, 2020

Neurofibromatosis Clinical Trials Consortium
Scott Plotkin, M.D., Ph.D., Massachusetts General Hospital, and Matthias Karajannis, M.D., M.S., New York University, the first and corresponding authors on the publication describing the study

The Neurofibromatosis Clinical Trials Consortium (NFCTC) researchers, led by study chair Dr. Scott Plotkin at Massachusetts General Hospital, recently published results from a Phase II evaluation of high-dose bevacizumab used as a therapy in neurofibromatosis type 2 (NF2) patients with vestibular schwannomas (VSs) in the Journal of Clinical Oncology. Bilateral VSs are a hallmark of NF2 and can lead to hearing loss and other complications. Bevacizumab is used for treatment of several types of cancer, often in combination with other therapeutics. It functions through inhibition of vascular endothelial growth factor A (VEGF-A), an important molecule in the growth of new blood vessels, which could prevent or slow the growth of tumors. This study, performed under a fiscal year 2011 (FY11) Department of Defense Neurofibromatosis Research Program (NFRP) award, used a higher dose of bevacizumab than previous studies to determine whether a higher dose would have a larger effect. 

The researchers enrolled children and adults with progressive VSs who were poor candidates for surgery or radiation treatment, and they evaluated the hearing response and radiographic response rates to the medication. Quality of life for patients was measured with the NF2 Impact on Quality of Life (NFTI-QOL) questionnaire and the Tinnitus Reaction Questionnaire before and after treatment. The NFTI-QOL assesses hearing, dizziness and balance, facial palsy, sight, mobility and walking, role and outlook on life, pain, and anxiety and depression. 

When compared to lower doses, high-dose bevacizumab seemed to be similarly effective at increasing hearing response and shrinking tumors, suggesting that the lower doses are adequate for treatment. Additionally, while tumor shrinkage was observed in adult patients on induction therapy, this was not observed in children on the same therapy. However, both adults and children reported improvements in quality of life, which indicates that treatments incorporating bevacizumab could be beneficial to children with NF2.

The NFCTC was established through FY05 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 9 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.

Investigators and staff of the Consortium

Publication:

Plotkin SR, Duda DG, Muzikansky A, et al. 2019. Multicenter, prospective, phase II and biomarker study of high-dose bevacizumab as induction therapy in patients with neurofibromatosis type 2 and progressive vestibular schwannoma. J Clin Oncol 37(35):3446-3454.

Links:

https://CDMRP.HEALTH.MIL/nfrp/consortium/nfrpctc

http://www.uab.edu/nfconsortium

Public and Technical Abstracts: Neurofibromatosis Clinical Consortium Award

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