This is a single center Phase 0 "window of opportunity" trial for the treatment of newly diagnosed, PRC2 deficient, primary malignant peripheral nerve sheath tumors (MPNSTs) with a short course of the combination of mirdametinib and vorinostat prior to the most appropriate standard of care treatment for their specific tumor (typically localized radiation followed by surgical resection). Four to eight patients, 12 years of age or older and meeting the study's biomarker inclusion criteria, would be enrolled onto this trial. After voluntary written consent (assent with parent consent for minors) the patient undergoes MRI and PET imaging of the tumor and a needle biopsy to collect tumor is performed. Patients with histone H3K27 trimethylation deficient MPNST, as confirmed by immunohistochemistry, receive a single 28-day course of mirdametinib and vorinostat at standard oral dosing for each. At day 26, 27, or 28 the patient returns to clinic for a research visit repeating the baseline MRI and PET imaging and the needle biopsy for tumor tissue. This ends direct study participation. The patient goes on to the most appropriate standard of care treatment for their MPNST. Information about the subsequent standard of care treatment is collected for the purposes of this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
short course of the combination of mirdametinib and vorinostat prior to the most appropriate standard of care treatment for the patient's specific tumor (typically localized radiation followed by surgical resection).
University of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGAssess the toxicity of the combination of mirdametinib and vorinostat in patients with NF1-associated high grade MPNSTs.
As a result of the vaccine, both unique CNS toxicity and edema have been previously observed as soon as 10 days from the initiation of therapy. Neurotoxicity ≤ Grade 3 is an expected risk of this treatment. This will be measured as the number of participants experiencing this adverse event.
Time frame: 48 months
Determine the response of therapeutic targets
measuring phospho-ERK and histone H3K27 acetylation in post-therapy tumor tissue as compared to pre-treatment tumor tissue.
Time frame: 48 months
Evaluate the utility of radiographic response to this regimen
using MRI and PET. Each patient will undergo MRI of the primary lesion and CT/PET scan for staging and assessment of FDG uptake in the tumor at diagnosis and after completing 28 days of therapy with mirdametinib and vorinostat. Each patient will have a diagnostic tumor biopsy performed as a condition of entry into the study and to measure specific molecular tumor markers. A second biopsy will be performed at the completion of protocol therapy to assess tumor response to the therapy and to see if the specific tumor markers have changed as a result of the therapy given.
Time frame: 48 months
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