NCT06693284 · University of Minnesota
A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST]
What this study is about
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 the usual treatment treatment for their specific tumor (typically localized radiation followed by surgical resection).
View original scientific description
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.
Interventions
DRUG
mirdametinib and vorinostat
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).
Primary outcome measures
Assess the toxicity of the combination of mirdametinib and vorinostat in patients with NF1-associated high grade MPNSTs.
Time frame: 48 months
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.
Determine the response of therapeutic targets
Time frame: 48 months
measuring phospho-ERK and histone H3K27 acetylation in post-therapy tumor tissue as compared to pre-treatment tumor tissue.
Evaluate the utility of radiographic response to this regimen
Time frame: 48 months
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Known Neurofibromatosis type 1 (NF-1) syndrome based on current diagnostic criteria.
- Diagnosis of suspected MPNST by PET or MRI imaging
- Confirmation of histone H3 lysine 27 trimethylation-negative MPSNT by immunohistochemistry
- Twelve years of age or older
- Complete blood count (CBC), platelet, liver and kidney function within institutional normal limits performed within 14 days of 1 st dose of study drug.
- Must be able to swallow capsules.
- Females of childbearing potential must use highly effective contraception (see inclusion criteria section) from the time of study enrollment through 6 months after the last dose of vorinostat and mirdametinib. Males with partners of childbearing potential must use highly effective contraception from the time of study enrollment through 3 months after the last dose of vorinostat.
- Provides voluntary written consent prior to any study related activities, with parental/guardian consent and assent for those 12 to 17 years of age at enrollment.
Exclusion criteria
- Pregnant or breastfeeding - females of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to the 1 st dose of the study drugs.
- Significant cardiac disease
- Significant eye disease
- Radiation therapy or chemotherapy in the past year.
Where
- Minneapolis, Minnesota
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 29, 2026 · Source of record for eligibility and locations