MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas
a study on Plexiform Neurofibroma Neurofibromatosis
Summary
- Eligibility
- for people ages 2 years and up (full criteria)
- Location
- at UC Davis UC Irvine UCLA
- Dates
- study startedcompletion around
Description
Summary
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.
Official Title
A Phase 2b Trial of the MEK 1/2 Inhibitor (MEKi) PD-0325901 in Adult and Pediatric Patients With Neurofibromatosis Type 1 (NF1)-Associated Inoperable Plexiform Neurofibromas (PNs) That Are Causing Significant Morbidity
Details
Neurofibromas are benign 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 deficits 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).
Keywords
Plexiform Neurofibroma, Neurofibromatosis Type 1 (NF1), Neurofibromatoses, Neurofibromatosis 1, PD-0325901, MEK Inhibitor, Neurofibroma, Mirdametinib, Mirdametinib (PD-0325901) oral capsule or dispersible tablet, Mirdametinib (PD-0325901)
Eligibility
You can join if…
Open to people ages 2 years and up
- 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.
You CAN'T join if...
- 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.
Locations
- UCLA Oncology Center
Los Angeles California 90095 United States - University of California - Irvine Health
Orange California 92868-3201 United States - University of California - Davis Comprehensive Cancer Center
Sacramento California 95817 United States - Children's Hospital Los Angeles
Los Angeles California 90027 United States - Children's Hospital of Orange County
Orange California 92868 United States - Lucile Packard Children's Hospital Stanford
Palo Alto California 94304 United States
Details
- Status
- in progress, not accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- SpringWorks Therapeutics, Inc.
- ID
- NCT03962543
- Phase
- Phase 2 research study
- Study Type
- Interventional
- Participants
- About 114 people participating
- Last Updated