Phase 2 Trial of Selumetinib for the Prevention of Plexiform Neurofibroma Growth and Morbidity in Neurofibromatosis Type 1

University of Alabama at Birmingham17 sites in 1 country200 target enrollmentAugust 27, 2025

Overview

Brief Summary

Plexiform neurofibromas (PN) are known to cause significant morbidity in children with NF1. The recent FDA approval for selumetinib in children 2 years and older with inoperable symptomatic PN was based on the finding that selumetinib shrinks the majority of PN in children with NF1 and results in clinically meaningful benefit such as improvement in pain or range of motion. However, many morbidities, such as blindness or nerve damage, cannot be fully reversed with PN shrinkage. Therefore, there remains a critical need in this patient population to determine if young participants with PN in high-risk locations may benefit from early medical intervention prior to the development of clinical problems. This study will determine whether participants with asymptomatic PN in high-risk locations can potentially benefit from early treatment with selumetinib.

Detailed Description

Plexiform neurofibromas (PN) are known to cause significant morbidity in children with NF1. The recent FDA approval for selumetinib in children 2 years and older with inoperable symptomatic PN was based on the finding that selumetinib shrinks the majority of PN in children with NF1 and results in clinically meaningful benefit such as improvement in pain or range of motion. However, many morbidities, such as blindness or nerve damage, cannot be fully reversed with PN shrinkage. Therefore, there remains a critical need in this patient population to determine if young participants with PN in high-risk locations may benefit from early medical intervention prior to the development of clinical problems. This study will determine whether participants with asymptomatic PN in high-risk locations can potentially benefit from early treatment with selumetinib. Other: This trial will be operated through the Neurofibromatosis Clinical Trials Consortium, funded by the Congressionally Directed Medical Research Program under the Department of Defense which consists of 24 sites throughout the United States. Intervention: Selumetinib (KoselugoTM) at the FDA approved dose of 25 mg/m2/dose PO BID. Study Duration: 7 years Partcipant Durations: 5 years

Registry

clinicaltrials.gov

Start Date

August 27, 2025

End Date

September 1, 2032

Last Updated

last month

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

University of Alabama at Birmingham

Responsible Party

Principal Investigator

Girish Dhall, MD

Chair of NFCTC

University of Alabama at Birmingham

Eligibility Criteria

Inclusion Criteria

•Inclusion Criteria:
•Age: \> 1 (\>12 months) and ≤8 years of age at the time of study enrollment.
•Diagnosis: Participants with a diagnosis of NF1 based on the 2021 revised consensus criteria \[52\] and
•No known PN (prior to enrollment on Part 1). Participants for whom there is clinical suspicion for a PN (e.g., subtle facial asymmetry or large overlying hyperpigmented area) may be included in the study after discussion with the Study Chair so long as they have not previously had an MRI of the region of concern and are otherwise asymptomatic.
•Physical exam at your institution within 1 year prior to consent.
•Written informed consent must be obtained from the legal guardians of all participants \<18 years of age.

Exclusion Criteria

•Presence of a known, symptomatic PN with or without previous MRI imaging.
•Patients who have had previous whole-body MRI (WBMRI) are excluded from the study. However, patients who have had regional MRI(s) for an indication other than a PN and did not have a PN identified on previous MRI may still be eligible for the study.
•Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol.
•Prior treatment with selumetinib or another specific MEK1/2 inhibitor.
•Evidence of an optic pathway or other low-grade glioma, high grade glioma, malignant peripheral nerve sheath tumor, or other cancer/tumor requiring treatment with chemotherapy, biologic therapy or radiation therapy.
•Ongoing radiation therapy, chemotherapy, hormonal therapy directed at a tumor, immunotherapy, or biologic therapy.
•Clinical judgement by the investigator that the patient should not participate in the study.
•Inclusion Criteria:
•Enrolled on Part 1 of this study and completed baseline WBMRI within 6 weeks of planned enrollment on Part
•A measurable (≥3 mL) PN in a high-risk location as defined below (this must be confirmed by Study Chair or a member of the Study Committee prior to enrollment on Part 2).