Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1

NCT06188741 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: IRB-300010135164893W81XWH-22-3-0001
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 15

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.

Conditions

Neurofibromatosis 1; Plexiform Neurofibroma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Progression free survival (PFS) in the group treated with selumetinib compared to those in the observation group

  60 months

Secondary Outcomes (2)

• Participants found to have a previously unknown measurable PN

  60 months

• PFS

  60 months

Study Arms (3)

Part 1: WBMRI for NF1 patients with no known PN

NO INTERVENTION

To assess the incidence of asymptomatic PN in any location in participants with NF1 and no known PN

Part 2: Treatment randomization to selumetinib vs observation

EXPERIMENTAL

To determine if selumetinib treatment prevents PN growth in young participants with asymptomatic tumors in high-risk locations

Drug: Selumetinib

Part 3: Part 2 participants with growing or symptomatic PN

EXPERIMENTAL

To assess the proportion of participants who are able to maintain tumor response after transition to an intermittent dosing schedule

Drug: Selumetinib

Interventions

Selumetinib DRUG

Selumetinib (KoselugoTM) at the FDA approved dose of 25 mg/m2/dose PO BID

Also known as: Koselugo

Part 2: Treatment randomization to selumetinib vs observation; Part 3: Part 2 participants with growing or symptomatic PN

Eligibility Criteria

• Age: 1 Year - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• PART 2:
• Enrolled on Part 1 of this study and completed baseline WBMRI within 6 weeks of planned enrollment on Part 2.
• 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).
• In the head or neck (with the exception of isolated scalp lesions) OR
• Within the brachial or lumbosacral plexus OR
• Adjacent to high-risk structure(s), defined as:
• Major ("named") blood vessel OR
• Major ("named") airway OR

Sponsors & Collaborators

• Children's Hospital of Philadelphia: collaborator
• University of Alabama at Birmingham: lead
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (15)

Childrens of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

University of Chicago

Chicago, Illinois, 63637, United States

RECRUITING

Riley Hospital for Children/Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21231, United States

RECRUITING

National Cancer Institute/ National Institutes of Health

Bethesda, Maryland, 20892, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University - St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229-, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Texas, Southwestern

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Neurofibromatosis 1; Neurofibroma, Plexiform

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Central Study Contacts

Karen Cole-Plourde, BA

CONTACT

2055141317; kplourde@uab.edu

Juliette Southworth, BS

CONTACT

2055298967; jsouthworth@uab.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of NFCTC

Model Details: Selumetinib (KoselugoTM) at the FDA approved dose of 25 mg/m2/dose PO BID

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 3, 2024
• Study Start: August 27, 2025
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2032
• Last Updated: May 29, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)