Rationale and Design of BeatNF2 Trial: A Clinical Trial to Assess the Efficacy and Safety of Bevacizumab in Patients with Neurofibromatosis Type 2 Related Vestibular Schwannoma

Overview

Journal Curr Oncol

Publisher MDPI

Specialty Oncology

Date 2021 Feb 12

PMID 33572546

Citations 6

Authors

Masazumi Fujii

Masao Kobayakawa

Kiyoshi Saito

Akihiro Inano

Akio Morita

Mitsuhiro Hasegawa

Akitake Mukasa

Takafumi Mitsuhara

Takeo Goto

Shigeru Yamaguchi

Takashi Tamiya

Hirofumi Nakatomi

Soichi Oya

Fumiaki Takahashi

Taku Sato

Mudathir Bakhit

The BeatNF Trial Investigators

Affiliations

Soon will be listed here.

Abstract

Neurofibromatosis type 2 (NF2) causes bilateral vestibular schwannomas (VSs), leading to deafness. VS is treated by surgery or radiation, but neither treatments prevent hearing loss. Bevacizumab was found to be effective in suppressing the tumor's growth and may help to improve hearing. We are conducting a randomized, double-blind, multicenter clinical trial to verify the efficacy and safety of bevacizumab in NF2-related VS. The primary objective is to evaluate the efficacy of bevacizumab in improving hearing in the affected ear. One of the secondary objectives is to evaluate bevacizumab's efficacy in rechallenge treatment in relapsed cases. Sixty patients will randomly receive either bevacizumab or a placebo and will be clinically observed for 48 weeks in the initial intervention phase. In the first half (24 weeks), they will receive either 5 mg/kg of bevacizumab or a placebo drug. In the second half, all patients will receive 5 mg/kg of bevacizumab. If hearing function deteriorated in a patient who had shown improvement during the first phase, a rechallenge dose with bevacizumab would be offered.

Citing Articles

Metastasis Associated in Colorectal Cancer 1 (MACC1) mRNA Expression Is Enhanced in Sporadic Vestibular Schwannoma and Correlates to Deafness.

Breun M, Flock K, Feldheim J, Nattmann A, Monoranu C, Herrmann P Cancers (Basel). 2023; 15(16).

PMID: 37627117 PMC: 10452285. DOI: 10.3390/cancers15164089.

Loss of social independence in patients with neurofibromatosis type 2: a follow-up study using a national registry in Japan.

Okoshi H, Yamauchi T, Suka M, Yanagisawa H, Fujii M, Nishigori C Environ Health Prev Med. 2023; 28:46.

PMID: 37599081 PMC: 10460997. DOI: 10.1265/ehpm.22-00222.

Current progress in genomics and targeted therapies for neurofibromatosis type 2.

Hiruta R, Saito K, Bakhit M, Fujii M Fukushima J Med Sci. 2023; 69(2):95-103.

PMID: 37468280 PMC: 10480513. DOI: 10.5387/fms.2023-05.

Tumor Biology and Microenvironment of Vestibular Schwannoma-Relation to Tumor Growth and Hearing Loss.

Tesarova M, Peterkova L, Stastna M, Kolar M, Lacina L, Smetana Jr K Biomedicines. 2023; 11(1).

PMID: 36672540 PMC: 9856152. DOI: 10.3390/biomedicines11010032.

A Critical Overview of Targeted Therapies for Vestibular Schwannoma.

Tamura R, Toda M Int J Mol Sci. 2022; 23(10).

PMID: 35628268 PMC: 9143502. DOI: 10.3390/ijms23105462.

References

Fujii M, Ichikawa M, Iwatate K, Bakhit M, Yamada M, Kuromi Y . Bevacizumab Therapy of Neurofibromatosis Type 2 Associated Vestibular Schwannoma in Japanese Patients. Neurol Med Chir (Tokyo). 2020; 60(2):75-82. PMC: 7040431. DOI: 10.2176/nmc.oa.2019-0194. View

Alanin M, Klausen C, Caye-Thomasen P, Thomsen C, Fugleholm K, Poulsgaard L . The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2. Eur Arch Otorhinolaryngol. 2014; 272(12):3627-33. DOI: 10.1007/s00405-014-3398-3. View

Morris K, Golding J, Blesing C, Evans D, Ferner R, Foweraker K . Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort. J Neurooncol. 2016; 131(1):117-124. DOI: 10.1007/s11060-016-2276-9. View

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

Sponghini A, Platini F, Rondonotti D, Soffietti R . Bevacizumab treatment for vestibular schwannoma in a patient with neurofibromatosis type 2: hearing improvement and tumor shrinkage. Tumori. 2015; 101(6):e167-70. DOI: 10.5301/tj.5000313. View

Blakeley J, Ye X, Duda D, Halpin C, Bergner A, Muzikansky A . Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2-Associated Vestibular Schwannomas. J Clin Oncol. 2016; 34(14):1669-75. PMC: 4872317. DOI: 10.1200/JCO.2015.64.3817. View

Yang J, Haworth L, Sherry R, Hwu P, Schwartzentruber D, Topalian S . A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003; 349(5):427-34. PMC: 2275324. DOI: 10.1056/NEJMoa021491. View

Gugel I, Grimm F, Liebsch M, Zipfel J, Teuber C, Kluwe L . Impact of Surgery on Long-Term Results of Hearing in Neurofibromatosis Type-2 Associated Vestibular Schwannomas. Cancers (Basel). 2019; 11(9). PMC: 6770212. DOI: 10.3390/cancers11091376. View

Vredenburgh J, Desjardins A, Herndon 2nd J, Marcello J, Reardon D, Quinn J . Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007; 25(30):4722-9. DOI: 10.1200/JCO.2007.12.2440. View

10.

Plotkin S, Merker V, Halpin C, Jennings D, McKenna M, Harris G . Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2: a retrospective review of 31 patients. Otol Neurotol. 2012; 33(6):1046-52. DOI: 10.1097/MAO.0b013e31825e73f5. View

11.

Kruyt I, Verheul J, Hanssens P, Kunst H . Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: a matched cohort study with sporadic vestibular schwannomas. J Neurosurg. 2017; 128(1):49-59. DOI: 10.3171/2016.9.JNS161463. View

12.

Friedman R, Goddard J, Wilkinson E, Schwartz M, Slattery 3rd W, Fayad J . Hearing preservation with the middle cranial fossa approach for neurofibromatosis type 2. Otol Neurotol. 2011; 32(9):1530-7. DOI: 10.1097/MAO.0b013e3182355855. View

13.

Phi J, Kim D, Chung H, Lee J, Paek S, Jung H . Radiosurgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2: tumor control and hearing preservation. Cancer. 2008; 115(2):390-8. DOI: 10.1002/cncr.24036. View

14.

Plotkin S, Duda D, Muzikansky A, Allen J, Blakeley J, Rosser T . 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. 2019; 37(35):3446-3454. PMC: 7098833. DOI: 10.1200/JCO.19.01367. View

15.

Mautner V, Nguyen R, Kutta H, Fuensterer C, Bokemeyer C, Hagel C . Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010; 12(1):14-8. PMC: 2940556. DOI: 10.1093/neuonc/nop010. View

16.

Bernardeschi D, Peyre M, Collin M, Smail M, Sterkers O, Kalamarides M . Internal Auditory Canal Decompression for Hearing Maintenance in Neurofibromatosis Type 2 Patients. Neurosurgery. 2015; 79(3):370-7. DOI: 10.1227/NEU.0000000000001125. View

17.

Hawasli A, Rubin J, Tran D, Adkins D, Waheed S, Hullar T . Antiangiogenic agents for nonmalignant brain tumors. J Neurol Surg B Skull Base. 2014; 74(3):136-41. PMC: 3709924. DOI: 10.1055/s-0033-1338262. View

18.

Otsuka G, Saito K, Nagatani T, Yoshida J . Age at symptom onset and long-term survival in patients with neurofibromatosis Type 2. J Neurosurg. 2003; 99(3):480-3. DOI: 10.3171/jns.2003.99.3.0480. View

19.

Plotkin S, Merker V, Muzikansky A, Barker 2nd F, Slattery 3rd W . Natural history of vestibular schwannoma growth and hearing decline in newly diagnosed neurofibromatosis type 2 patients. Otol Neurotol. 2013; 35(1):e50-6. DOI: 10.1097/MAO.0000000000000239. View

20.

Sun S, Liu A . Long-term follow-up studies of Gamma Knife surgery for patients with neurofibromatosis Type 2. J Neurosurg. 2014; 121 Suppl:143-9. DOI: 10.3171/2014.8.GKS141503. View