Phase II Study of Binimetinib in Children and Adults With NF1 Plexiform Neurofibromas (NF108-BINI)

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ClinicalTrials.gov Identifier: NCT03231306

Recruitment Status : Active, not recruiting

First Posted : July 27, 2017

Last Update Posted : December 21, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

Array BioPharma

Pacific Pediatric Neuro-Oncology Consortium

Information provided by (Responsible Party):

Bruce Korf, MD, University of Alabama at Birmingham

No Study Results Posted on ClinicalTrials.gov for this Study

About Study Results Reporting on ClinicalTrials.gov

Recruitment Status :	Active, not recruiting
Estimated Primary Completion Date :	December 31, 2025
Estimated Study Completion Date :	December 31, 2026

Publications:

Wu J, Williams JP, Rizvi TA, Kordich JJ, Witte D, Meijer D, Stemmer-Rachamimov AO, Cancelas JA, Ratner N. Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell. 2008 Feb;13(2):105-16. doi: 10.1016/j.ccr.2007.12.027.

Kebudi R, Cakir FB, Gorgun O. Interferon-alpha for unresectable progressive and symptomatic plexiform neurofibromas. J Pediatr Hematol Oncol. 2013 Apr;35(3):e115-7. doi: 10.1097/MPH.0b013e318270cd24.

Citak EC, Oguz A, Karadeniz C, Okur A, Memis L, Boyunaga O. Management of plexiform neurofibroma with interferon alpha. Pediatr Hematol Oncol. 2008 Sep;25(7):673-8. doi: 10.1080/08880010802315983.

Jakacki RI, Dombi E, Potter DM, Goldman S, Allen JC, Pollack IF, Widemann BC. Phase I trial of pegylated interferon-alpha-2b in young patients with plexiform neurofibromas. Neurology. 2011 Jan 18;76(3):265-72. doi: 10.1212/WNL.0b013e318207b031.

Widemann BC, Arceci RJ, Jayaprakash N, Fox E, Zannikos P, Goodspeed W, Goodwin A, Wright JJ, Blaney SM, Adamson PC, Balis FM. Phase 1 trial and pharmacokinetic study of the farnesyl transferase inhibitor tipifarnib in children and adolescents with refractory leukemias: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Feb;56(2):226-33. doi: 10.1002/pbc.22775. Epub 2010 Sep 21.

Widemann BC, Salzer WL, Arceci RJ, Blaney SM, Fox E, End D, Gillespie A, Whitcomb P, Palumbo JS, Pitney A, Jayaprakash N, Zannikos P, Balis FM. Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. J Clin Oncol. 2006 Jan 20;24(3):507-16. doi: 10.1200/JCO.2005.03.8638.

Babovic-Vuksanovic D, Widemann BC, Dombi E, Gillespie A, Wolters PL, Toledo-Tamula MA, O'Neill BP, Fox E, MacDonald T, Beck H, Packer RJ. Phase I trial of pirfenidone in children with neurofibromatosis 1 and plexiform neurofibromas. Pediatr Neurol. 2007 May;36(5):293-300. doi: 10.1016/j.pediatrneurol.2007.01.009.

Babovic-Vuksanovic D, Ballman K, Michels V, McGrann P, Lindor N, King B, Camp J, Micic V, Babovic N, Carrero X, Spinner R, O'Neill B. Phase II trial of pirfenidone in adults with neurofibromatosis type 1. Neurology. 2006 Nov 28;67(10):1860-2. doi: 10.1212/01.wnl.0000243231.12248.67. Epub 2006 Oct 11.

Kim A, Dombi E, Tepas K, Fox E, Martin S, Wolters P, Balis FM, Jayaprakash N, Turkbey B, Muradyan N, Choyke PL, Reddy A, Korf B, Widemann BC. Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas. Pediatr Blood Cancer. 2013 Mar;60(3):396-401. doi: 10.1002/pbc.24281. Epub 2012 Sep 7.

Lasater EA, Bessler WK, Mead LE, Horn WE, Clapp DW, Conway SJ, Ingram DA, Li F. Nf1+/- mice have increased neointima formation via hyperactivation of a Gleevec sensitive molecular pathway. Hum Mol Genet. 2008 Aug 1;17(15):2336-44. doi: 10.1093/hmg/ddn134. Epub 2008 Apr 28.

McCormick F. Ras signaling and NF1. Curr Opin Genet Dev. 1995 Feb;5(1):51-5. doi: 10.1016/s0959-437x(95)90053-5.

Sherman LS, Atit R, Rosenbaum T, Cox AD, Ratner N. Single cell Ras-GTP analysis reveals altered Ras activity in a subpopulation of neurofibroma Schwann cells but not fibroblasts. J Biol Chem. 2000 Sep 29;275(39):30740-5. doi: 10.1074/jbc.M001702200.

Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003 Jan;3(1):11-22. doi: 10.1038/nrc969.

Weiss B, Bollag G, Shannon K. Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet. 1999 Mar 26;89(1):14-22.

Wu J, Dombi E, Jousma E, Scott Dunn R, Lindquist D, Schnell BM, Kim MO, Kim A, Widemann BC, Cripe TP, Ratner N. Preclincial testing of sorafenib and RAD001 in the Nf(flox/flox) ;DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging. Pediatr Blood Cancer. 2012 Feb;58(2):173-80. doi: 10.1002/pbc.23015. Epub 2011 Feb 11.

Kissil JL, Blakeley JO, Ferner RE, Huson SM, Kalamarides M, Mautner VF, McCormick F, Morrison H, Packer R, Ramesh V, Ratner N, Rauen KA, Stevenson DA, Hunter-Schaedle K, North K. What's new in neurofibromatosis? Proceedings from the 2009 NF Conference: new frontiers. Am J Med Genet A. 2010 Feb;152A(2):269-83. doi: 10.1002/ajmg.a.33189.

Yang FC, Ingram DA, Chen S, Zhu Y, Yuan J, Li X, Yang X, Knowles S, Horn W, Li Y, Zhang S, Yang Y, Vakili ST, Yu M, Burns D, Robertson K, Hutchins G, Parada LF, Clapp DW. Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow. Cell. 2008 Oct 31;135(3):437-48. doi: 10.1016/j.cell.2008.08.041.

Jessen WJ, Miller SJ, Jousma E, Wu J, Rizvi TA, Brundage ME, Eaves D, Widemann B, Kim MO, Dombi E, Sabo J, Hardiman Dudley A, Niwa-Kawakita M, Page GP, Giovannini M, Aronow BJ, Cripe TP, Ratner N. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors. J Clin Invest. 2013 Jan;123(1):340-7. doi: 10.1172/JCI60578. Epub 2012 Dec 10.

Chang T, Krisman K, Theobald EH, Xu J, Akutagawa J, Lauchle JO, Kogan S, Braun BS, Shannon K. Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice. J Clin Invest. 2013 Jan;123(1):335-9. doi: 10.1172/JCI63193. Epub 2012 Dec 10. Erratum In: J Clin Invest. 2016 Jan;126(1):404.

Nutakki K, Hingtgen CM, Monahan P, Varni JW, Swigonski NL. Development of the adult PedsQL neurofibromatosis type 1 module: initial feasibility, reliability and validity. Health Qual Life Outcomes. 2013 Feb 21;11:21. doi: 10.1186/1477-7525-11-21.

Rosser T, Packer RJ. Neurofibromas in children with neurofibromatosis 1. J Child Neurol. 2002 Aug;17(8):585-91; discussion 602-4, 646-51. doi: 10.1177/088307380201700808.

Le LQ, Parada LF. Tumor microenvironment and neurofibromatosis type I: connecting the GAPs. Oncogene. 2007 Jul 12;26(32):4609-16. doi: 10.1038/sj.onc.1210261. Epub 2007 Feb 12.

Prada CE, Jousma E, Rizvi TA, Wu J, Dunn RS, Mayes DA, Cancelas JA, Dombi E, Kim MO, West BL, Bollag G, Ratner N. Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition. Acta Neuropathol. 2013 Jan;125(1):159-68. doi: 10.1007/s00401-012-1056-7. Epub 2012 Oct 26.

Wolkenstein P, Zeller J, Revuz J, Ecosse E, Leplege A. Quality-of-life impairment in neurofibromatosis type 1: a cross-sectional study of 128 cases. Arch Dermatol. 2001 Nov;137(11):1421-5. doi: 10.1001/archderm.137.11.1421.

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