Mirdametinib to Reduce the Size of Large/Giant Congenital Melanocytic Nevi in Children, Adolescents and Young Adults

NCT07891286 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10002599002599-C
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Large and giant congenital melanocytic nevi (LGCMN) are dark birthmarks (moles). They can grow to 8 inches or more across. People with LGCMN have an increased risk of getting skin cancer or problems with the nervous system. Researchers want to find out if a drug approved for a different use (mirdametinib) can shrink the size of LGCMN. Objective: To test mirdametinib in people with LGCMN. Eligibility: People aged 3 to 40 years with LGCMN. Design: Participants will be screened. Their LGCMN sites will be measured and photographed. They will have blood tests, an eye exam, and tests of their heart function. They will also have:

• An exam of their nervous system: Their muscle strength, ability to feel and touch, balance, alertness, and other skills will be tested.
• Magnetic resonance imaging (MRI) scan: They will lie on a bed that slides into a tube; the scan will use large magnets to create images of their brain and spinal cord.
• Skin biopsy: A small sample of their skin may be taken.
• VECTRA scan: This is a 3-dimensional imaging system that takes pictures of all of the skin all at once. Mirdametinib will be either pills or capsules that are taken by mouth. Participants will take the drug in 4-week cycles. They will take the pills 2 times a day for 3 weeks with 1 week off. Participants may continue taking the drug for 2 years. They will have clinic visits 12 times while taking the drug. Imaging scans and other tests will be repeated. Participants will continue to have checkups every 6 months for 3 more years.

Conditions

LGCMN; Large and Giant Congenital Melanocytic Nevi; NF1; Solid Tumor; Pediatric Tumors; Neurocutaneous Melanocytosis; Congenital Melanocytic Nevus; Arachnoid Cysts; Astrocytoma; Ependymoma; Melanoma

Keywords

Mirdametinib; MEK Inhibitor; MAPK; VECTRA; pERK; Large and giant congenital melanocytic nevi; LGCMN

Outcome Measures

Primary Outcomes (1)

• Determine whether treatment with mirdametinib results in objective decreases in the largest diameter of LGCMN

  Difference between the diameter (largest dimension) of the LGCMN recorded during the 24-cycle study period). The average difference, as well as the 95% confidence interval, the median, and the interquartile range, will be reported. The difference will be tested for statistical significance using a paired t-test; with adjustments for distribution, if needed.

  Pre-treatment and for up to 24 months on treatment.

Secondary Outcomes (6)

• Feasibility of evaluating LGCMN thickness by MRI

  Pre-treatment and for up to 24 months on treatment.

• Determine whether mirdametinib treatment reduces the number of satellite nevi (nevi in addition to the largest target nevus) when they are present

  Pre-treatment and for up to 24 months on treatment.

• Evaluate the safety of mirdametinib in participants with LGCMN

  Pre-treatment and for up to 24 months on treatment, including post-safety follow-up.

• Determine whether mirdametinib treatment results in improvement of itching QOL measures in participants with LGCMN

  Pre-treatment and for up to 24 months on treatment/end of treatment.

• Evaluate the feasibility of evaluating pERK as a pharmacodynamic marker for mirdametinib response in serial biopsies of LGCMN

  Pre-treatment, cycles 2 and 13 on treatment, and end of treatment.

Study Arms (1)

Arm 1

EXPERIMENTAL

Mirdametinib will be administered orally, twice daily on an intermittent dosing schedule (3 weeks on, 1 week off). The dosage will be 2-4 mg/m2/dose.

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

Mirdametinib dosage will be 2-4 mg/m2/dose orally twice daily.

Arm 1

Eligibility Criteria

• Age: 3 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have a clinical diagnosis of a large and giant congenital melanocytic nevi (LGCMN).
• Participants must have a documented history of somatic pathogenic or likely pathogenic variation in NRAS or BRAF, or a pathogenic fusion in which one of the fusion partners is ALK, NTRK1, BRAF, or RAF1. Participants who do not have documented history will be tested by NSR device (via next-generation sequencing panel TruSight(TM) Oncology 500)
• Participants must have: at least one nevus \> 20 cm
• at least one nevus with a projected adult diameter \> 20 cm (participants \< 18 years old).
• Note: Participants who have had prior surgical treatment of their LGCMN, but the remaining nevus has a diameter \> 20 cm, are eligible for enrollment.
• Age \>= 3 years and \<= 40 years old.
• Participants must have a Body Surface Area (BSA) \>= 0.4 m\^2.
• Clinical performance status: Karnofsky \>= 70% (\>= 16 years); Lansky scale \>=70% (\< 16 years).
• Participants must have adequate organ and marrow function as defined below:
• Hemoglobin \>= 11 g/dL
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin \<= 1.5 X institutional upper limit of normal (ULN) for age. Note: 3 X ULN for age for participants with Gilbert syndrome
• Aspartate Aminotransferase (AST) \<= 3 X institutional ULN
• Alanine Aminotransferase (ALT) \<= 3 X institutional ULN

You may not qualify if:

• Participants who are receiving any investigational agents within the 30 days prior to the study treatment initiation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to mirdametinib.
• Prior treatment with mirdametinib or another specific MEK1/2 inhibitor.
• 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).
• Ophthalmologic findings secondary to long-standing optic pathway glioma or NCM (such as visual loss, optic nerve pallor, or strabismus) will NOT be considered a significant abnormality for the purposes of the study.
• Cardiac conditions:
• Heart failure (any New York Heart Association \[NYHA\] class)
• Myocardial infarction, severe/unstable angina, coronary or peripheral artery bypass graft placement, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism within 6 months prior to starting study treatment.
• Refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption of mirdametinib.
• Any unresolved chronic toxicity grade \>= 2 per CTCAE from previous therapy, except for alopecia.
• History of renal transplant.
• Major surgery within 4 weeks prior to starting study treatment.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurocutaneous melanosis; Arachnoid Cysts; Astrocytoma; Ependymoma; Melanoma

Interventions

mirdametinib

Condition Hierarchy (Ancestors)

Cysts; Neoplasms; Central Nervous System Cysts; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Marielle E Yohe, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NIH Clinical Center Office of Patient Re

CONTACT

(800) 411-1222; ccopr@nih.gov

Marielle E Yohe, M.D.

CONTACT

(240) 760-7436; marielle.yohe@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2026
• First Posted: October 23, 2026
• Study Start (Estimated): January 4, 2027
• Primary Completion (Estimated): January 4, 2029
• Study Completion (Estimated): January 4, 2032
• Last Updated: October 23, 2026

Record last verified: 2026-10-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
• Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians. The scientific data will be findable by key words or MeSH terms used during publication of manuscripts.

Locations

US (1)