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Early selumetinib to try to prevent plexiform neurofibromas in young children with NF1

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

Phase 2 Interventional University of Alabama at Birmingham · NCT06188741

This trial will see if giving selumetinib to young children with NF1 who are at high risk can prevent or slow the development of plexiform neurofibromas.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment200 (estimated)
Ages1 Year to 8 Years
SexAll
SponsorUniversity of Alabama at Birmingham Academic / other
Drugs / interventionsselumetinib, chemotherapy, immunotherapy, radiation
Locations13 sites (Birmingham, Alabama and 12 other locations)
Trial IDNCT06188741 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional study gives oral selumetinib (25 mg/m2 twice daily) to children with NF1 who are at high risk for plexiform neurofibromas and follows them prospectively for clinical and imaging signs of tumor development. Participants will be enrolled at sites in the Neurofibromatosis Clinical Trials Consortium and undergo regular MRI and clinical exams to monitor for new or growing plexiform neurofibromas and for drug safety. The trial includes long-term follow-up (participants up to five years, overall study duration seven years) to detect prevention of morbidity that may not be reversible after tumors enlarge. Safety monitoring will focus on known selumetinib side effects and age-appropriate developmental assessments.

Who should consider this trial

Good fit: Young children (older than 12 months up to 8 years) with a clinical diagnosis of NF1 who are judged to be at high risk for plexiform neurofibromas in critical locations and who do not have known symptomatic PN are ideal candidates.

Not a fit: Children who already have known, symptomatic plexiform neurofibromas or established irreversible morbidity (for example blindness or major nerve injury) are unlikely to benefit from this preventive approach.

Why it matters

Potential benefit: If successful, early selumetinib could prevent or limit plexiform neurofibroma growth in critical locations and reduce irreversible complications such as vision loss or nerve damage.

How similar studies have performed: Selumetinib has previously shown tumor shrinkage and clinical benefit in children (≥2 years) with inoperable symptomatic plexiform neurofibromas leading to FDA approval, but using it as an early preventive treatment in asymptomatic high-risk children is a novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
PART 1:

Inclusion Criteria:

1. Age: \> 1 (\>12 months) and ≤8 years of age at the time of study enrollment.
2. Diagnosis: Participants with a diagnosis of NF1 based on the 2021 revised consensus criteria \[52\] and
3. 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.
4. Physical exam at your institution within 1 year prior to consent.
5. Written informed consent must be obtained from the legal guardians of all participants \<18 years of age.

Exclusion Criteria:

1. Presence of a known, symptomatic PN with or without previous MRI imaging.
2. 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.
3. Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol.
4. Prior treatment with selumetinib or another specific MEK1/2 inhibitor.
5. 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.
6. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at a tumor, immunotherapy, or biologic therapy.
7. Clinical judgement by the investigator that the patient should not participate in the study.

PART 2:

Inclusion Criteria:

1. Enrolled on Part 1 of this study and completed baseline WBMRI within 6 weeks of planned enrollment on Part 2.
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:

     1. Major ("named") blood vessel OR
     2. Major ("named") airway OR
     3. Hollow viscus OR
     4. Spinal cord and foramina OR
     5. Vital Organs (including heart, lungs, liver, spleen, etc.)
3. Body Surface Area (BSA): BSA ≥ 0.55 m2 \[pending availability of granule formulation\].
4. 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.
5. Able to swallow whole capsules \[Pending availability of granule formulation\].
6. Hematologic Function: Absolute neutrophil count ≥1200/µL, hemoglobin ≥9g/dL, and platelets ≥100,000/µL (without transfusions).
7. 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.
8. 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
9. Cardiac Function:

   1. 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).
   2. EKG with QTC or QTcF ≤450 msec.
10. 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.
11. Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.
12. 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.

Exclusion Criteria:

1. 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.
2. Ongoing radiation therapy, chemotherapy, hormonal therapy, immunotherapy, or biologic therapy directed at a tumor.
3. Prosthesis, orthopedic implant, or dental braces that would interfere with volumetric analysis of target PN on MRI.
4. Use of an investigational agent within the past 30 days.
5. 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.
6. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
7. Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
8. 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.
9. Participants not achieving adequate blood pressure despite antihypertensive therapy for control of blood pressure.
10. Cardiac conditions:

    1. Known inherited coronary disease
    2. Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)
    3. Prior or current cardiomyopathy
    4. Severe valvular heart disease
    5. History of atrial fibrillation
11. Ophthalmologic conditions:

    1. Current or past history of central serous retinopathy or retinal pigment epithelial detachment (RPED).
    2. Current or past history of retinal vein occlusion.
    3. History of radiation therapy that included the orbit in the field of treatment.
    4. 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.
    5. Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.
    6. 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.
12. 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.
13. Recent major surgery within a minimum of 4 weeks prior to starting study treatment.
14. Any unresolved chronic toxicity with CTCAE grade ≥ 2 from previous therapy, except for alopecia.
15. 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:

Inclusion Criteria:

1. 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).
2. Body Surface Area (BSA): BSA ≥ 0.55 m2 \[pending availability of granule formulation\].
3. 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.
4. Able to swallow whole capsules \[Pending availability of granule formulation\].
5. Hematologic Function: Absolute neutrophil count ≥1200/µL, hemoglobin ≥9g/dL, and platelets ≥100,000/µL (without transfusions).
6. 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.
7. 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
8. Cardiac Function:

   1. 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).
   2. EKG with QTC or QTcF ≤450 msec.
9. 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.
10. Willingness to avoid excessive sun exposure and use adequate sunscreen protection if sun exposure is anticipated.
11. 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.

Exclusion Criteria:

1. 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.
2. Ongoing radiation therapy, chemotherapy, hormonal therapy, immunotherapy, or biologic therapy directed at a tumor.
3. Prosthesis, orthopedic implant, or dental braces that would interfere with volumetric analysis of target PN on MRI.
4. 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.
5. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
6. Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
7. 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.
8. Participants not achieving adequate blood pressure despite antihypertensive therapy for control of blood pressure.
9. Cardiac conditions:

   1. Known inherited coronary disease
   2. Symptomatic heart failure (NYHA Class II-IV prior or current cardiomyopathy, or severe valvular heart disease)
   3. Prior or current cardiomyopathy
   4. Severe valvular heart disease
   5. History of atrial fibrillation
10. Ophthalmologic conditions:

    1. Current or past history of central serous retinopathy or retinal pigment epithelial detachment (RPED).
    2. Current or past history of retinal vein occlusion.
    3. History of radiation therapy that included the orbit in the field of treatment.
    4. 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.
    5. Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.
    6. 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.
11. 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.
12. Recent major surgery within a minimum of 4 weeks prior to starting study treatment.
13. Any unresolved chronic toxicity with CTC AE grade ≥ 2 from previous therapy, except for alopecia.
14. 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.

Where this trial is running

Birmingham, Alabama and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Neurofibromatosis 1Plexiform Neurofibroma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.