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MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
Trial Status: closed to accrual
This study evaluates mirdametinib (PD-0325901) in the treatment of symptomatic inoperable
neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants
will receive mirdametinib (PD-0325901). Eligible participants may continue in a long-term
follow-up phase.
Inclusion Criteria
Participant has documented NF1 mutation or a diagnosis of neurofibromatosis type 1 (NF1) using National Institute of Health (NIH) Consensus Conference criteria inclusive of the presence of a plexiform neurofibroma (PN).
Participant has a PN that is causing significant morbidity.
Participant has a PN that cannot be completely surgically removed.
Participant has a target tumor that is amenable to volumetric MRI analysis.
Participant is willing to undergo a tumor biopsy pre and post treatment if ≥ 18 years of age.
Participant has adequate organ and bone marrow function. Key
Exclusion Criteria
Participant has abnormal liver function or history of liver disease.
Participant has lymphoma, leukemia or any malignancy within the past 5 years (except for resected basal/squamous skin carcinomas without metastases within 3 years).
Participant has breast cancer within 10 years.
Participant has active optic glioma or other low-grade glioma requiring treatment.
Participant has abnormal QT interval corrected or other heart disease within 6 months.
Participant has a history of retinal pathology, risk factors for retinal vein occlusion or has a history of glaucoma.
Participant has known malabsorption syndrome or gastrointestinal conditions that would impair absorption of mirdametinib (PD-0325901).
Participant has received NF1 PN-targeted therapy within 45 days.
Participant previously received or is currently receiving therapy with mirdametinib (PD-0325901) or any other MEK1/2 inhibitor.
Participant has received radiation therapy within 6 months or has received radiation to the orbit at any time.
Participant is unable to undergo or tolerate MRI.
Participant has active bacterial, fungal or viral infection.
Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year.
Additional locations may be listed on ClinicalTrials.gov for NCT03962543.
Locations matching your search criteria
United States
Alabama
Birmingham
University of Alabama at Birmingham Cancer Center
Status: Active
Name Not Available
Pennsylvania
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: Active
Name Not Available
Neurofibromas are non-malignant peripheral nerve sheath tumors, which are classified as
plexiform neurofibromas (PNs) if they extend longitudinally along a nerve and involve
multiple fascicles. PNs are a major cause of morbidity and disfigurement in individuals
with NF1, and as the tumor growth progresses, can cause a multitude of clinical problems
including pain and impaired physical function. PNs have the potential to undergo
malignant transformation to Malignant Peripheral Nerve Sheet Tumors (MPNST).
Mirdametinib (PD-0325901) is an orally delivered, highly selective small-molecule
inhibitor of the dual specificity kinases, MEK1 and MEK2 (MAPK/ERK Kinase) which prevents
the phosphorylation and subsequent activation of mitogen-activated protein kinase (MAPK).
Previous studies of mirdametinib (PD-0325901) demonstrated PN shrinkage and sustained
inhibition of pERK. Reduced tumor volume indicated that cell proliferation or cell death
may be altered in PNs with administration of mirdametinib (PD-0325901).
