At a glance
ClinicalIndex Comparison Record- ✓Confirmed diagnosis of NF1 by NIH Consensus Conference clinical criteria OR documented constitutional NF1 mutation in a CLIA/CAP certified lab
- ✓Plexiform neurofibroma(s) that are progressive OR causing significant morbidity (airway/vessel compromise, nerve compression with loss of function, major deformity, significant disfigurement, or pain)
- ✓Measurable plexiform neurofibroma(s) amenable to volumetric MRI analysis, with target lesion visible on at least 3 consecutive slices and at least 3 mL in volume (or <3 cm longest diameter if discussed with Study Chair)
- ✓Age ≥16 years at study entry
- ✕Prior treatment with any MEK inhibitor
- ✕Active optic glioma or other low-grade glioma requiring treatment; prior orbital radiation at any time
- ✕Glaucoma, intraocular pressure >21 mmHg, or significant abnormality on ophthalmologic examination
- ✕Malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy requiring treatment in the last 12 months
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Phase 2 Trial of the MEK Inhibitor PD-0325901 in Adolescents and Adults With NF1-Associated Morbid Plexiform Neurofibromas
In Brief
A Phase 2 clinical trial evaluating PD-0325901 for Neurofibromatosis Type 1 and Growing or Symptomatic, Inoperable PN. Completed, enrolled 19 participants across 11 sites.
Detailed Summary
This phase II open label study will evaluate adolescents (≥ 16 years of age) and adults with neurofibromatosis type-1 (NF1) and plexiform neurofibromas treated with the MEK inhibitor PD-0325901. The primary aim of the study will be to assess quantitative radiographic response in a target lesion. Subjects will receive PD-0325901 by mouth on a bid dosing schedule of 2 mg/m2/dose with a maximum dose of 4 mg bid. Each course is 4 weeks duration, and subjects will receive drug on a 3 week on/1 week off schedule. Subjects may receive additional courses beyond course 8 only if there is at least 15% reduction in volume of the target tumor. Subjects who have a 20% or greater reduction in target tumor volume at the end of 12 courses can continue on therapy for up to an additional year (maximum of 24 total courses). However, subjects who do not achieve at least 15% reduction in volume of the target tumor after 8 courses (\~8 months) will be considered treatment failures and taken off study. The Primary purpose of this protocol is to determine whether PD-0325901 results in objective radiographic responses based on volumetric MRI measurements in adolescents and adults with NF1 and growing or symptomatic inoperable PN. There are several secondary aims of this protocol: To evaluate the feasibility and toxicity of chronic PD-0325901 administration in this patient population To estimate the objective response rate of up to 2 non-target plexiform neurofibromas to PD-0325901 by MRI To characterize the pharmacokinetic profile of PD-0325901 when administered to this patient population To evaluate quality of life and pain during treatment with PD-0325901