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Neurofibromatosis 1Phase 2NF114NCT06188741

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

A Phase 2 study testing Selumetinib in people with Neurofibromatosis 1 and Plexiform Neurofibroma, run by University of Alabama at Birmingham at 15 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 1 year to 8 years
Conditions the study is for
Neurofibromatosis 1, Plexiform Neurofibroma
What is being tested?
Selumetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
15 sitesUnited States
Study dates
27 Aug 2025to 1 Sep 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 8 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
  • Enrolled on Part 1 of this study and completed baseline WBMRI within 6 weeks of planned enrollment on Part 2.
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  • 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
  • Hollow viscus OR
  • Spinal cord and foramina OR
  • Vital Organs (including heart, lungs, liver, spleen, etc.)
  • Body Surface Area (BSA): BSA ≥ 0.55 m2 [pending availability of granule formulation].
  • Performance status: Lansky performance ≥70%. Participants who are wheelchair bound because of paralysis or immobility secondary to a non-PN related manifestation of NF1 (such as tibial pseudarthrosis or severe scoliosis) should be considered ambulatory when they are in their wheelchair.
  • Able to swallow whole capsules [Pending availability of granule formulation].
  • Hematologic Function: Absolute neutrophil count ≥1200/µL, hemoglobin ≥9g/dL, and platelets ≥100,000/µL (without transfusions).
  • Hepatic Function: Bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST/ALT within ≤ 3 x upper limit of normal.
  • Renal Function: Creatinine clearance or radioisotope GFR ≥60ml/min/1.73 m2 or a normal serum creatinine based on age, described in the table below.
  • Age (years) Maximum Serum Creatinine (mg/dL)
  • ≤5 0.8 >5 to ≤10 1.0 >10 to ≤15 1.2 >15 1.5
  • Cardiac Function:
  • Normal ejection fraction (ECHO or cardiac MRI) ≥ 53% (or the institutional normal; if a range is given then the upper value of the range will be used).
  • EKG with QTC or QTcF ≤450 msec.
  • Adequate Blood Pressure defined as:
  • A blood pressure (BP) ≤ the 95th percentile for age, height, and gender. Adequate blood pressure can be achieved using medication for treatment of hypertension. Participants must be on stable antihypertensive regimen for at least 30 days prior to study entry.
  • Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.
  • Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g., grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism.
  • Enrolled on Part 2 of this study and had PN growth >20% OR development of PN related symptom(s) while on observation portion of Part 2 (including the first 2 years for the observation arm OR during first year of observation after treatment with selumetinib).
  • Body Surface Area (BSA): BSA ≥ 0.55 m2 [pending availability of granule formulation].
  • Performance status: Lansky performance ≥70%. Participants who are wheelchair bound because of paralysis or immobility secondary to a non-PN related manifestation of NF1 (such as tibial pseudarthrosis or severe scoliosis) should be considered ambulatory when they are in their wheelchair.
  • Able to swallow whole capsules [Pending availability of granule formulation].
  • Hematologic Function: Absolute neutrophil count ≥1200/µL, hemoglobin ≥9g/dL, and platelets ≥100,000/µL (without transfusions).
  • Hepatic Function: Bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and AST/ALT within ≤ 3 x upper limit of normal.
  • Renal Function: Creatinine clearance or radioisotope GFR ≥60mL/min/1.73 m2 or a normal serum creatinine based on age, described in the table below.
  • Age (years) Maximum Serum Creatinine (mg/dL)
  • ≤5 0.8 >5 to ≤10 1.0 >10 to ≤15 1.2 >15 1.5
  • Cardiac Function:
  • Normal ejection fraction (ECHO or cardiac MRI) ≥ 53% (or the institutional normal; if a range is given then the upper value of the range will be used).
  • EKG with QTC or QTcF ≤450 msec.
  • Adequate Blood Pressure defined as:
  • A blood pressure (BP) ≤ the 95th percentile for age, height, and gender. Adequate blood pressure can be achieved using medication for treatment of hypertension. Participants must be on stable antihypertensive regimen for at least 30 days prior to study entry.
  • Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.
  • Willingness to avoid the ingestion of grapefruit and Seville oranges (as well as other products containing these fruits, e.g., grapefruit juice or marmalade) during the study, as these may affect selumetinib metabolism.

Who cannot join

  • 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.
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  • Clinical judgement by the investigator that the patient should not participate in the study.
  • PART 2:
  • 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, immunotherapy, or biologic therapy directed at a tumor.
  • Prosthesis, orthopedic implant, or dental braces that would interfere with volumetric analysis of target PN on MRI.
  • Use of an investigational agent within the past 30 days.
  • Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded.
  • Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
  • Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to initiation of therapy.
  • Participants not achieving adequate blood pressure despite antihypertensive therapy for control of blood pressure.
  • Cardiac conditions:
  • Known inherited coronary disease
  • Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)
  • Prior or current cardiomyopathy
  • Severe valvular heart disease
  • History of atrial fibrillation
  • Ophthalmologic conditions:
  • Current or past history of central serous retinopathy or retinal pigment epithelial detachment (RPED).
  • Current or past history of retinal vein occlusion.
  • History of radiation therapy that included the orbit in the field of treatment.
  • Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Participants with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the Study Chair.
  • Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.
  • Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) will NOT be considered a significant abnormality for the purposes of the study.
  • Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.
  • Recent major surgery within a minimum of 4 weeks prior to starting study treatment.
  • Any unresolved chronic toxicity with CTCAE grade ≥ 2 from previous therapy, except for alopecia.
  • Receiving herbal supplements or medications known to be strong or moderate inhibitors or inducers of the cytochrome P450 (CYP)2C19 and CYP3A4 enzymes or fluconazole unless such products can be safely discontinued at least 14 days or 5 half-lives (whichever is longer) before the first dose of study medication.
  • PART 3:
  • 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, immunotherapy, or biologic therapy directed at a tumor.
  • Prosthesis, orthopedic implant, or dental braces that would interfere with volumetric analysis of target PN on MRI.
  • Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses, or renal transplant, including any patient known to have hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) will be excluded.
  • Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
  • Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to initiation of therapy.
  • Participants not achieving adequate blood pressure despite antihypertensive therapy for control of blood pressure.
  • Cardiac conditions:
  • Known inherited coronary disease
  • Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)
  • Prior or current cardiomyopathy
  • Severe valvular heart disease
  • History of atrial fibrillation
  • Ophthalmologic conditions:
  • Current or past history of central serous retinopathy or retinal pigment epithelial detachment (RPED).
  • Current or past history of retinal vein occlusion.
  • History of radiation therapy that included the orbit in the field of treatment.
  • Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Participants with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after discussion with the study chair.
  • Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.
  • Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) will NOT be considered a significant abnormality for the purposes of the study.
  • Known severe hypersensitivity to selumetinib or any excipient of selumetinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.
  • Recent major surgery within a minimum of 4 weeks prior to starting study treatment.
  • Any unresolved chronic toxicity with CTC AE grade ≥ 2 from previous therapy, except for alopecia.
  • Receiving herbal supplements or medications known to be strong or moderate inhibitors or inducers of the cytochrome P450 (CYP)2C19 and CYP3A4 enzymes or fluconazole unless such products can be safely discontinued at least 14 days or 5 half-lives (whichever is longer) before the first dose of study medication.

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Karen Cole-Plourde, BA contact

2055141317

kplourde@uab.edu

Juliette Southworth, BS contact

2055298967

jsouthworth@uab.edu

15 sites in 1 country

United States15 sites, 15 recruiting

  • Johns Hopkins University

    Baltimore, Maryland, 21231

    Joshua Roberts, PhD, (410) 955-6827, jrobe112@jhmi.edu

    Jaishri Blakeley, MD

    Recruiting

  • National Cancer Institute/ National Institutes of Health

    Bethesda, Maryland, 20892

    Hemaxi Patel, 240-243-8838, hemaxi.patel@nih.gov

    Brigitte Widemann, MD

    Recruiting

  • Childrens of Alabama

    Birmingham, Alabama, 35233

    Manjul Virmani, BS, 205-638-6259, manjulvirmani@uabmc.edu

    Britney McKenzie, 205-638-6259, britneymckenzie@uabmc.edu

    Recruiting

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

    Olivia Clancy, 617-919-0291, Olivia.Clancy@childrens.harvard.edu

    Nicole Ullrich, MD, PhD

    Recruiting

  • Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

    Kelly Bruno, (312)227-4810, kbruno@luriechildrens.org

    Miriam Bornhorst, MD

    Recruiting

  • University of Chicago

    Chicago, Illinois, 63637

    Cynthia MacKenzie, 773-702-6487, cmackenzie@peds.bsd.uchicago.edu

    James Tonsgard, MD

    Recruiting

  • Cincinnati Childrens Hospital Medical Center

    Cincinnati, Ohio, 45229-

    Lori Backus, 513-517-2068, Peter.deBlank@cchmc.org; lori.backus@cchmc.org

    Andrea Gross, MD

    Recruiting

  • University of Texas, Southwestern

    Dallas, Texas, 75390

    Laura Klesse, MD, PhD, (214) 456-2382, NFCMCUT@groups.utsouthwestern.edu

    Laura Klesse, MD, PhD

    Recruiting

  • Riley Hospital for Children/Indiana University

    Indianapolis, Indiana, 46202

    Steven Rhodes, MD, PhD, (317) 948-6641, RileyNFnurse@iuhealth.org

    Steven Rhodes, MD, PhD

    Recruiting

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

    Tena Rosser, MD, 323-361-2471, trosser@chla.usc.org

    Martha Arellano-Garcia, MS, 323-361-5812, margarcia@chla.usc.edu

    Recruiting

  • Stanford University

    Palo Alto, California, 94304

    Cynthia Campen, MD, 650-497-8953, ccampen@stanford.edu

    Cynthia Campen, MD

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Ratnakar Patti, 267-426-5503, pattir@email.chop.edu

    Michael Fisher, MD

    Recruiting

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Meg Connors, 507-266-2275, rstclinicalgenomics@mayo.edu

    Radhika Dhamija, MBBS

    Recruiting

  • Washington University - St. Louis

    St Louis, Missouri, 63110

    Amy Armstrong, MD, 314-454-6018, armstrongae@wustl.edu

    Amy Armstrong, MD

    Recruiting

  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

    Benjamin Siegel, MD, 202-476-5181, NF@childrensnational.org

    Benjamin Siegel, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the 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

Being tested
Selumetinib
Medical subject headings
Neurofibromatosis 1, Neurofibroma, Plexiform

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SelumetinibDrug

    Also called Koselugo

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

Study groups in NCT06188741
Study groupRoleWhat they receive
Part 1: WBMRI for NF1 patients with no known PNNo interventionTo assess the incidence of asymptomatic PN in any location in participants with NF1 and no known PN
Part 2: Treatment randomization to selumetinib vs observationExperimentalTo determine if selumetinib treatment prevents PN growth in young participants with asymptomatic tumors in high-risk locations
Receives: Drug: Selumetinib
Part 3: Part 2 participants with growing or symptomatic PNExperimentalTo assess the proportion of participants who are able to maintain tumor response after transition to an intermittent dosing schedule
Receives: Drug: Selumetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

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

    Measured: 60 months

Secondary outcomes (2)

  1. Participants found to have a previously unknown measurable PN

    Proportion of participants found to have a previously unknown measurable PN in any location on WBMRI imaging

    Measured: 60 months

  2. PFS

    1. PFS through one year after transitioning from continuous to an intermittent dosing schedule

    Measured: 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2024
  2. Study start27 Aug 2025
  3. Primary completion1 Sep 2031 (estimated)
  4. Study completion1 Sep 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Selumetinib (KoselugoTM) at the FDA approved dose of 25 mg/m2/dose PO BID
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06188741
Sponsor's protocol ID
IRB-300010135
Other IDs
164893, W81XWH-22-3-0001
Acronym
NF114
Status last verified
Sep 2025
First submitted
18 Dec 2023
Last updated
29 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Selumetinib in people with Neurofibromatosis 1 and Plexiform Neurofibroma, run by University of Alabama at Birmingham at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 60 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Karen Cole-Plourde, BA (2055141317, kplourde@uab.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: 60 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06188741.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.

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