Actively Recruiting
Phase 1/2 Trial of Mirdametinib in Patients With MAPK Pathway Mutant Central Nervous System Tumors
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-05-13
26
Participants Needed
7
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Memorial Sloan Kettering Cancer Center
Lead Sponsor
S
SpringWorks Therapeutics, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating whether mirdametinib is a safe and effective treatment for Central Nervous System tumors, including glioma and neurohistiocytosis. This phase 1/2 trial focuses on patients with MAPK pathway mutant CNS tumors to better understand the drug's impact on these conditions. The study is sponsored by Memorial Sloan Kettering Cancer Center and aims to measure the best overall neurologic response rate within one year. Participants are divided into two main groups. Eleven patients with refractory neurohistiocytosis will receive continuous cycles of mirdametinib. Meanwhile, 30 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to either receive perioperative mirdametinib for five days before surgery or no drug before surgery. After surgery, all glioma participants will take mirdametinib twice daily continuously until disease progression or clinical changes occur. During the study, participants will undergo regular evaluations including neurological assessments and monitoring of disease progression via imaging scans. Researchers will collect data on safety, tolerability, and treatment response. The study includes scheduled visits, laboratory tests, and performance status assessments. Participation will continue until disease progression or other criteria require stopping treatment, with ongoing monitoring throughout the trial period.
CONDITIONS
Brief Title
A Study of Mirdametinib in People With Central Nervous System Tumors
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Be older than 18 years of age
- Have a Karnofsky Performance Status of 70% or higher, or an ECOG Performance Status of 2 or less
- Able to understand and provide written informed consent, or have a legally authorized representative
- Adequate bone marrow function: ANC greater than 1,500/mm3, platelet count over 100,000/mm3, hemoglobin above 9.0 mg/dL
- Adequate liver function: total bilirubin within 1.5 times the upper limit of normal or baseline, AST and ALT within 3 times the upper limit of normal or baseline
- Adequate kidney function: creatinine clearance of 50 mL/min or higher
- Adequate heart function: left ventricular ejection fraction over 50%, corrected QT interval under 480 ms
- Women of childbearing potential must have a negative pregnancy test before treatment
- Patients with prior or concurrent malignancy allowed if it does not interfere with the study
- Recovery from prior radiotherapy toxicities to grade 1 or less
- For Neurohistiocytosis cohort: documented or likely MAPK pathway mutation, confirmed disease, and measurable neurologic disease
- For Glioma cohort: somatic or germline NF1 mutation, confirmed glioma diagnosis, measurable MRI-evaluable disease, recurrent or progressive disease after prior treatment, surgery indicated but not urgent, expected survival over 3 months
You will not qualify if you...
- Pregnant or nursing
- Participating in another interventional study at the same time
- Received tumor-directed therapy within 28 days before starting mirdametinib
- Taking medications that strongly induce CYP3A
- History of allergic reaction to mirdametinib or similar compounds
- Serious active infections without at least 48 hours fever-free
- Uncontrolled or severe medical conditions
- Significant active heart disease within 6 months prior to treatment
- Significant active eye disease within 6 months prior to treatment
- Any condition or therapy that might interfere with study results or participant safety
- For Neurohistiocytosis cohort: documented driver mutations outside the MAPK pathway
- Female participants of childbearing potential must agree to use contraception during and after treatment; male participants with partners of reproductive potential must also use contraception during and after treatment
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 5 days
Participants in Cohort B may receive perioperative mirdametinib for 5 days before surgery.
1 visit (in-person) for perioperative treatment
Duration - 1 day
Participants in Cohort B undergo standard of care surgery for their glioma.
1 visit (in-person) for surgery
Duration - Continuous until clinical or radiographic progression
Participants receive mirdametinib twice daily continuously after surgery or as continuous treatment cycles until disease progression or discontinuation.
Regular visits as per protocol for treatment monitoring
Trial Site Locations
Total: 7 locations
1
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
2
Memorial Sloan Kettering Monmouth (Limited protocol activities)
Middletown, New Jersey, United States, 07748
Actively Recruiting
3
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, United States, 07645
Actively Recruiting
4
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
Commack, New York, United States, 11725
Actively Recruiting
5
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, United States, 10604
Actively Recruiting
6
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, United States, 10065
Actively Recruiting
7
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Rockville Centre, New York, United States, 11570
Actively Recruiting
Research Team
A
Anna Piotrowski, MD
E
Eli Diamond, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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