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
This study evaluates PD-0325901 in the treatment of symptomatic inoperable neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PNs). All participants will receive PD-0325901.
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 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 PD-0325901.
2 Years and up
Accepting Healthy Volunteers?
- 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.
- Participant can swallow capsules whole.
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 PD-0325901
- Participant has received NF1 PN-targeted therapy within 28 days.
- 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.