LGCMNPhase 2NCT07891286
Mirdametinib to Reduce the Size of Large/Giant Congenital Melanocytic Nevi in Children, Adolescents and Young Adults
A Phase 2 study testing Mirdametinib in people with LGCMN and Large and Giant Congenital Melanocytic Nevi, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 40 years
- Conditions the study is for
- LGCMN, Large and Giant Congenital Melanocytic Nevi, NF1
- What is being tested?
- Mirdametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2027to 4 Jan 2032
- Phase
- Phase 2
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 3 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
- OR
- 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.
Show all 40Show fewer
- 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
- Estimated creatinine clearance >= 30 mL/min/1.73 m^2 as calculated per the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (>= 18 years old) or Chronic Kidney Disease in Children Under 25 (CKiD U25) in (< 18 years old)
- Cardiac function: Normal ejection fraction (echocardiogram [ECHO] or cardiac MRI), defined as ejection fraction (EF) >= 53%; normal QTc interval, defined as QTcF <= 450 msec
- Blood pressure (BP):
- Adults (>= 18 years old): BP <= 130 systolic and <= 80 diastolic
- Children (< 18 years old): BP <= the 95th percentile for age, height, and sex
- Adequate blood pressure can be achieved using medication for the treatment of hypertension.
- --Serum creatine phosphokinase (CPK) <= 2.5 X institutional ULN
- Participants with neurocutaneous melanocytosis must be asymptomatic and have nonprogressive disease.
- Participants with seizure disorder may be enrolled if on anticonvulsants, and there has been no change to their anticonvulsant medication in the 4 weeks prior to the study treatment initiation, and the participant has been seizure-free during that time.
- Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy must have an undetectable viral load.
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load and be on suppressive therapy, if indicated.
- Participants with evidence of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and be cured or on suppressive therapy, if indicated.
- Women who are nursing or plan to nurse a child must agree to discontinue/postpone nursing while taking mirdametinib and until 1 week after the administration of the last dose of mirdametinib.
- Women of child-bearing potential (WOCBP) must agree to use an effective contraception (barrier, hormonal, intrauterine device, surgical sterilization, continuous abstinence) while taking mirdametinib and until 6 weeks after administration of the last dose of mirdametinib. A participant may request a male partner to use an effective form of contraception to fulfill this requirement.
- Note: WOCBP defined as:
- biologically female sex with a uterus and at least one ovary who is at least Tanner Stage 3, AND
- entered puberty and has not completed menopause AND
- does not meet the definition of female participant who cannot get pregnant as follows:
- has undergone a hysterectomy OR
- has undergone a bilateral oophorectomy OR
- has completed menopause defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml or 6 weeks postsurgical OR
- has not gone through menarche or reached Tanner Stage 3
- Men (biologically male sex) must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) while taking mirdametinib and until 3 months after administration of the last dose of mirdametinib. A participant may request a female partner to use an effective form of contraception to fulfill this requirement. Men must not freeze or donate sperm within the same period.
- -Ability of participant or parent/guardian to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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
Show all 19Show fewer
- 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.
- Prior history of melanoma or other malignancy.
- Active infection (currently on treatment with anti-microbials).
- Positive serum or urine beta-human chorionic gonadotropin (beta-HCG) pregnancy test performed at screening.
- Uncontrolled, symptomatic intercurrent illness evaluated by medical history, physical exam, lab evaluations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of 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.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937, ncimo_referrals@mail.nih.gov
About this study
Official title: A Phase II Study to Evaluate the Use of the MEK Inhibitor Mirdametinib to Reduce the Size of Large/Giant Congenital Melanocytic Nevi in Children, Adolescents and Young Adults
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.
Read more
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.
Read the detailed description
Background:
- Large and giant congenital melanocytic nevi (LGCMN) are melanocytic nevi that originate in utero and that will reach at least 20 cm in diameter in adult life.
- Patients with LGCMN have an increased lifetime risk of developing malignant melanoma, with most cases (70%) being diagnosed before puberty.
- There is no consensus regarding the optimal treatment of LGCMN.
- LGCMN are associated with somatic hotspot variants in the oncogene NRAS, resulting in increased mitogen-activated protein kinase (MAPK) pathway activity.
- Mirdametinib is a highly selective non-ATP-competitive inhibitor of MEK1 and MEK2, which inhibits the phosphorylation of the MAP kinases ERK1 and ERK2, leading to decreased tumor cell growth.
- Mirdametinib is indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
- Mirdametinib has a generally manageable safety profile.
Objective:
-To determine whether treatment with mirdametinib results in objective decreases in the largest diameter of LGCMN.
Eligibility:
-Individuals >=3 years and <=40 years with LGCMN who have adequate organ function and performance status.
Design:
- This is a single-stage, single-arm, open-label, single-institution phase II study of mirdametinib in participants with LGCMN.
- Patient-reported outcomes will be evaluated at regular intervals.
- The LGCMN diameter will be measured both by providers with expertise in this condition and by the VECTRA Whole Body 3D imaging system at baseline and then at regular intervals.
- The feasibility of using Magnetic Resonance Imaging (MRI) to estimate the dermal thickness of LGCMN will be assessed.
- Since there are very limited data on the timing and magnitude of changes in these LGCMN in the literature, the degree of changes identified will be important to document in this hypothesis-generating trial to inform any subsequent trials, regardless of the magnitude of the changes identified.
- Conditions
- LGCMN, Large and Giant Congenital Melanocytic Nevi, NF1, Solid Tumor, Pediatric Tumors, Neurocutaneous Melanocytosis
- Being tested
- Mirdametinib
- Keywords
- Mirdametinib, MEK Inhibitor, MAPK, VECTRA, pERK, Large and giant congenital melanocytic nevi, LGCMN
- Medical subject headings
- Neurocutaneous melanosis, Arachnoid Cysts, Astrocytoma, Ependymoma, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MirdametinibDrug
Mirdametinib dosage will be 2-4 mg/m2/dose orally twice daily.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Mirdametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Pre-treatment and for up to 24 months on treatment.
Secondary outcomes (6)
Feasibility of evaluating LGCMN thickness by MRI
The percent of participants with measurable LGCMN thickness (>1 cm) on MRI will be reported as a summary statistic.
Measured: 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
Participants with satellite nevi, in addition to the sentinel LGCMN required for study enrollment, will undergo standardized counting of the satellite nevi. The percentage of participants with satellite nevi at baseline will be reported as a summary statistic. For participants with satellite nevi at baseline, the average and 95% confidence interval of the number of satellite nevi at baseline and at the end of treatment, as well as the median and interquartile range, will be reported.
Measured: Pre-treatment and for up to 24 months on treatment.
Evaluate the safety of mirdametinib in participants with LGCMN
Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade per CTCAE.
Measured: 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
The average scores as well as the 95% confidence interval will be reported.
Measured: 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
The reported endpoints will be the percentage of participants undergoing at least 2 biopsies and the percentage of biopsies for which pERK was able to be determined via Luminex assay. These will be reported as endpoint/summary statistics.
Measured: Pre-treatment, cycles 2 and 13 on treatment, and end of treatment.
Determine whether cutaneous or extracutaneous melanoma occurs in participants with LGCMN while on or after mirdametinib treatment
The reported endpoint will be the incidence of melanoma for participants on this study. This will be accomplished by calculating the proportion of participants enrolled who are diagnosed with melanoma over the course of the study. Results will be provided on a descriptive basis.
Measured: Pre-treatment and for up to 24 months on treatment, including through up to 5 years of post-treatment follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2026
- Study start4 Jan 2027 (estimated)
- Primary completion4 Jan 2029 (estimated)
- Study completion4 Jan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LGCMNStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Marielle E Yohe, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07891286
- Sponsor's protocol ID
- 10002599
- Other IDs
- 002599-C
- Status last verified
- 20 Oct 2026
- First submitted
- 22 Oct 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.