MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas

Summary

Background: Neurofibromatosis type 1 (NF1) is a disorder that can cause plexiform neurofibromas (PNs). These are tumors that grow along nerves. Some PNs cause serious health problems. PNs often can t be operated on because of their large size, location, or number. There are no effective treatments known for people with NF1 and PNs. Researchers want to test if the drug selumetinib (AZD6244 hydrogen sulfate) causes PNs to shrink or slows down their growth. Objectives: To test if selumetinib helps treat PNs. To test how the body handles selumetinib and how it affects peoples symptoms. Eligibility: People ages 18 and older with NF1, with an inoperable PN that causes morbidity or is growing Design: Participants will be screened with: Medical history and physical exam Blood, urine, and heart tests Eye exam MRI: They lie in a machine that takes pictures of the body. PN biopsy: A small piece of the tumor is removed by a large needle. Questionnaires Participants will swallow selumetinib capsules every 12 hours for several 28-day cycles. The capsules are taken with a full glass of water on an empty stomach. Participants may have only water for 2 hours before and 1 hour after each dose. Participants will keep a drug diary. They will continue taking the drug as long as they tolerate it and their disease doesn t progress. Participants will have several visits throughout the study. These will include repeats of the screening tests. Participants will have a final visit after they stop taking selumetinib.

Timeline

Start

2016-01-07

Primary completion

2028-01-01

Completion

2030-01-01

Publications

• Gross AM, O'Sullivan Coyne G, Dombi E, Tibery C, Herrick WG, Martin S, Angus SP, Shern JF, Rhodes SD, Foster JC, Rubinstein LV, Baldwin A, Davis C, Dixon SAH, Fagan M, Ong MJ, Wolters PL, Tamula MA, Reid O, Sankaran H, Fang F, Govindharajulu JP, Browne AT, Kaplan RN, Heisey K, On TJ, Xuei X, Zhang X, Johnson BC, Parchment RE, Clapp DW, Srivastava AK, Doroshow JH, Chen AP, Widemann BC. Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial. Nat Med. 2025 Jan;31(1):105-115. doi: 10.1038/s41591-024-03361-4. Epub 2025 Jan 6.
• Curry BP, Alvarez R, Widemann BC, Johnson M, Agarwal PK, Lehky T, Valera V, Chittiboina P. Robotic Nerve Sheath Tumor Resection With Intraoperative Neuromonitoring: Case Series and Systematic Review. Oper Neurosurg. 2022 Feb 1;22(2):44-50. doi: 10.1227/ONS.0000000000000051.
• Herrick WG, Kilpatrick CL, Hollingshead MG, Esposito D, O'Sullivan Coyne G, Gross AM, Johnson BC, Chen AP, Widemann BC, Doroshow JH, Parchment RE, Srivastava AK. Isoform- and Phosphorylation-specific Multiplexed Quantitative Pharmacodynamics of Drugs Targeting PI3K and MAPK Signaling in Xenograft Models and Clinical Biopsies. Mol Cancer Ther. 2021 Apr;20(4):749-760. doi: 10.1158/1535-7163.MCT-20-0566. Epub 2021 Feb 3.

Drugs

Indications