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Neurofibromatosis 1 (NF1)Phase 2NF118NCT07521657

Efficacy of Mirdametinib Alone or Combination With Radiotherapy for Germline and Sporadic NF1-Altered High-Grade Glioma

A Phase 2 study testing mirdametinib with radiation and mirdametinib in people with Neurofibromatosis 1 (NF1), run by University of Alabama at Birmingham at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a phase 2, open label, parallel multi-arm study of mirdametinib in combination with radiation in participants with recurrent sporadic glioblastoma (GBM) harboring NF1 alterations (Cohort 1); participants with NF1 with a newly diagnosed GBM (Cohort 2); mirdametinib alone in other NF1-associated High-Grade… Read more about this study

Who is it for?
Ages 12 to 89 years
Conditions the study is for
Neurofibromatosis 1 (NF1)
What is being tested?
mirdametinib with radiation and mirdametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteUnited States
Study dates
1 Jan 2027to 1 Jan 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 12 to 89 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Tumor diagnosis:
  • Cohort 1 (applies to non-NF1 related GBM): GBM, IDH-wildtype grade 4 of brain or spinal cord by WHO 2021 central nervous system tumor diagnostic criteria52 that is recurrent after irradiation and first-line chemotherapy (if appropriate). Any number of prior recurrences is acceptable. Tumor Next Generation Sequencing (NGS) must demonstrate at least one pathogenic/likely pathogenic NF1 alteration (known or suspected to confer loss of function) at time of first or recurrent surgery that could putatively confer loss-of-function.
  • Cohort 2 (applies to participants with NF1): Pathology consistent with GBM, IDH-wildtype grade 4 by WHO 2021 CNS tumor diagnostic criteria or HGG with somatic TP53 mutation (brain or spinal cord). Participants may not have received any therapy beyond surgical resection for the target HGG.
  • Cohort 3 (applies to participants with NF1): HGAP (including low-grade glioma classified as HGAP by methylation profiling) or other HGG not meeting criteria for Cohort 2. Participants may not have received prior therapy for the HGG.
  • Neurofibromatosis 1:
  • Cohort 1: Participants may not have a diagnosis of NF1.
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  • Cohort 2/3: All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.
  • Age: Cohort 1: Participants must be ≥ 18 years of age at the time of enrollment. Cohorts 2/3: Participants must be ≥ 12 years of age at the time of enrollment.
  • Performance Level: Participants must have performance status of >= 60 using Karnofsky for participants aged >= 16 years, and Lansky for participants < 16 years of age.
  • Cohort 3: Participants must have measurable disease by RANO 2.0 HGG or LGG criteria on baseline MRI.
  • Participants must have available archival tissue from the HGG or GBM of interest. Tissue blocks strongly preferred and will be returned to sending site at end of study. Exceptions may be made following discussion with study team if tissue has been exhausted and methylation profiling already performed.
  • Organ Function Requirements:
  • Adequate bone marrow function defined as:
  • Absolute neutrophil count > 1,000/mcL
  • Platelets > 100,000/mcL
  • Hemoglobin > 9 g/dL
  • Adequate renal function defined as:
  • Creatinine ≤ 1.5x institutional upper limit of normal based on age/gender OR
  • Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • Adequate liver function defined as:
  • Total bilirubin (sum of conjugated + unconjugated) <=1.5x upper limit of normal (ULN) for age (for participants with Gilbert's disease ≤3x ULN), and
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) < 2.5x the upper limit of normal (ULN).
  • PT/INR and partial thromboplastin time (PTT) test < 1.5x the laboratory ULN
  • CPK level ≤ 1.5x institutional ULN
  • Blood pressure within upper limit of normal as defined below. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 30 days of enrollment.
  • In adolescents, a blood pressure (BP) ≤ 90th percentile for age, height, and sex.
  • In adults (>=18 years of age), a systolic blood pressure consistently ≤150 mmHg and a diastolic pressure consistently ≤ 100 mmHg.
  • The following intervals from previous treatments are required to be eligible for all cohorts:
  • 12 weeks from an anti-VEGF therapy
  • 4 weeks from a nitrosourea chemotherapy
  • 3 weeks from a non-nitrosourea chemotherapy
  • 2 weeks or 5 half-lives from any investigational (not FDA-approved) agents
  • 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., erlotinib, hydroxychloroquine, etc.)
  • The following intervals from previous radiation are required to be eligible for each cohort:
  • Cohort 1: 24 weeks from prior radiation for the same tumor.
  • Cohort 2: 24 weeks from prior radiation for any other tumor. Note: Participants who received prior radiation for which the expected new prescription isodose field will overlap with the high dose field will be excluded.
  • Cohort 3: 12 weeks from any radiation therapy.
  • Written informed consent must be obtained from all participants (>18 years of age) or their legal guardians (if the participant is <18 years of age).
  • Participants must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to baseline MRI. Topical and inhaled steroid treatment is allowed.
  • Sexually active fertile participants and their partners must agree to use highly effective methods of contraception e.g., hormonal oral contraception, injectables, intrauterine device, surgical sterilization including vasectomy, or hormonal implant with barrier methods (male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 weeks after the last dose of study treatment. Barrier methods alone are insufficient. True sexual abstinence is an acceptable method of birth control for both men and women. Persons of childbearing potential will be given a pregnancy test within 72 hours prior to the first dose of study treatment and must have a negative urine or serum pregnancy test.
  • Female participants must agree not to harvest or donate eggs (ova, oocytes) and male participants must agree to not harvest or donate sperm for the purpose of reproduction during the treatment period and for at least 6 months after the last dose of study treatment. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment.

Who cannot join

  • Tumor positive for pathogenic IDH-mutation, H3.1 or H3.3 mutation, or BRAF alteration.
  • Participant has not recovered to ≤ Grade 1 non-hematologic toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (≤ Grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll.
  • Prior MEK inhibitor therapy:
  • Cohort 1: Prior MEK inhibitor therapy contraindicated
  • Cohorts 2/3: Prior MEK inhibitor therapy to target glioma contraindicated (even if the target tumor was previously suspected or biopsy-proven low-grade glioma). No oral MEK inhibitor therapy in the past 12 months for other manifestations of NF1 (including non-target glioma).
  • Topical MEK inhibitor within 12 months is not an exclusion but cannot be continued while on study.
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  • Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) ≤ 180 days prior to start date;
  • Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2);
  • Left ventricular ejection fraction (LVEF) < 50% as determined by MUGA or ECHO;
  • Baseline QTc interval > 450 msec;
  • History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia).
  • Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (≤ 90 days) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs.
  • History of recent (≤ 90 days) thromboembolic or cerebrovascular event such as transient ischemic attack, cerebrovascular accident, or hemodynamically significant (massive or sub-massive) deep vein thrombosis or pulmonary emboli (DVT/PE). Note: Participants with DVT/PE that does not result in hemodynamic instability may enroll as long as they are anticoagulated for at least 4 weeks.
  • Other Malignancies:
  • Cohort 1: Participants must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Participants with other malignancies must be disease-free for > 2 years.
  • Cohorts 2/3: Participants must have no current or prior diagnosis of malignant peripheral nerve sheath tumor or other malignancy requiring treatment in the last 2 years. A stable or previously treated LGG is acceptable.
  • Ophthalmologic conditions:
  • Current or history of central serous retinopathy.
  • Current or history of retinal vein occlusion.
  • 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 orbital plexiform neurofibromas should have IOP measured prior to enrollment.
  • Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study.
  • Note: Mild and controlled/stable age-related macular degeneration or non-proliferative diabetic retinopathy may be acceptable at the investigator's discretion after consultation with the ophthalmologist.
  • Participants with any other significant abnormality on ophthalmic examination should be discussed with the Study Chair for potential eligibility.
  • Other clinically significant disorders that would preclude safe study participation, including:
  • Active infection,
  • Poorly controlled HIV. HIV testing will not be required as part of this trial, unless HIV is clinically suspected,
  • Poorly controlled Hepatitis B or Hepatitis C
  • Pregnant or lactating women.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Current use of a prohibited medication (including herbal medications, supplements, or foods), or use of a prohibited medication ≤ 7 days prior to the start of study treatment.
  • Use of any medications or substances that are strong inhibitors of breast cancer resistance protein (BCRP) < 14 days prior to the study treatment initiation.
  • Participants who have other medical, social or concurrent challenges that are likely to negatively impact their ability to meet all of the trial obligations and therefore may increase the risk of safe participation in the study.

Trial locations and contacts

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

Juliette Southworth, BS contact

2055298967

jsouthworth@uab.edu

Karen Cole-Plourde, BA contact

2055141317

kplourde@uab.edu

United States1 site

  • Childrens of Alabama

    Birmingham, Alabama, 34294

    NFCTC Operations Center, 205-638-6259, nfcop@uab.edu

    Girish Dhall, MD

Other trials in United States

About this study

This is a phase 2, open label, parallel multi-arm study of mirdametinib in combination with radiation in participants with recurrent sporadic glioblastoma (GBM) harboring NF1 alterations (Cohort 1); participants with NF1 with a newly diagnosed GBM (Cohort 2); mirdametinib alone in other NF1-associated High-Grade Gliomas (Cohort 3).

Read the detailed description

Cohorts 1 and 2: Eligible participants will receive radiotherapy concurrently with twice daily mirdametinib. Mirdametinib will continue after completion of radiation in continuous 28-day cycles with treatment lasting up to 24 cycles. MR imaging to assess response will be performed 4 weeks after completion of radiation therapy, and every 2 months thereafter using Response Assessment in Neuro-Oncology (RANO) 2.0 enhancing criteria.

Cohort 3: Eligible participants will receive twice-daily mirdametinib in 28-day cycles for 6 cycles. MR imaging to assess response by Response Assessment in Neuro-Oncology (RANO) 2.0 non-enhancing criteria will be performed every 3 months thereafter to determine radiographic response. Participants with ongoing benefit may remain on therapy for up to 24 cycles following evaluation of the primary endpoint as determined by the treating physician.

Being tested
mirdametinib with radiation, mirdametinib
Keywords
Neurofibromatosis 1, NF1, gliomas, glioblastoma, High-Grade Gliomas (HHG), High-Grade Astrocytoma with Piloid Features (HGAP)
Medical subject headings
Neurofibromatosis 1, Glioma, Glioblastoma

What participants receive

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

  • mirdametinib with radiationCombination product

    Participants in Cohorts 1 and 2 will receive mirdametinib in combination with radiation therapy followed by mirdametinib alone.

  • mirdametinibDrug

    Participants in Cohort 3 will receive mirdametinib alone.

Study groups in NCT07521657
Study groupRoleWhat they receive
Cohort 1: Recurrent, sporadic glioblastoma (not NF1)ExperimentalParticipants with recurrent sporadic glioblastoma (GBM) harboring NF1 alterations will receive mirdametinib and radiation.
Receives: Combination Product: mirdametinib with radiation
Cohort 2: New diagnosed glioblastoma with no prior therapy (NF1 participants only)ExperimentalNF1 participants with new glioblastoma (GBM) will receive mirdametinib and radiation.
Receives: Combination Product: mirdametinib with radiation
Cohort 3: HGAP or HGG not meeting criteria for Cohort 2 (NF1 participants only)ExperimentalNF1 participants with High-Grade Astrocytoma with Piloid Features (HGAP) or other NF1-associated HGG not meeting criteria for Cohort 2 will receive mirdametinib alone.
Receives: Drug: mirdametinib

What is being measured

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

  1. Cohort 1

    Estimate overall survival at 12 months in participants with recurrent sporadic GBM harboring an NF1 alteration treated with repeat irradiation in combination with mirdametinib.

    Measured: From treatment to 12 months

  2. Cohort 2

    Estimate overall survival at 18 months in participants with a newly-diagnosed NF1-associated GBM treated with irradiation in combination with mirdametinib in Cohort 2.

    Measured: From treatment to 18 months

  3. Cohort 3

    Estimate response rate at six months in participants with germline NF1 and HGAP or a non-GBM high grade glioma. Tumor response is based on MRI imaging per RANO 2.0 guidelines.

    Measured: From treatment to 6 months

Timeline

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

  1. First posted13 Apr 2026
  2. Study start1 Jan 2027 (estimated)
  3. Primary completion1 Jan 2031 (estimated)
  4. Study completion1 Jan 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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07521657
Sponsor's protocol ID
IRB-300016184
Other IDs
W81XWH2230001, OSP:000551073, CTA00000011
Acronym
NF118
Status last verified
Sep 2026
First submitted
3 Apr 2026
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing mirdametinib with radiation and mirdametinib in people with Neurofibromatosis 1 (NF1), run by University of Alabama at Birmingham at 1 site 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 41 inclusion and 33 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: opening soon, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 Juliette Southworth, BS (2055298967, jsouthworth@uab.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1 (time frame: From treatment to 12 months). The study lists 3 primary outcomes in all. 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 NCT07521657.

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 5 Oct 2026.

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