A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST]

Last updated: May 28, 2026
Sponsor: University of Minnesota
Overall Status: Active - Recruiting

Phase

1

Condition

Sarcoma

Infantile Fibrosarcoma

Brain Cancer

Treatment

mirdametinib and vorinostat

Clinical Study ID

NCT06693284
2022LS040
  • Ages > 12
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

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 byimmunohistochemistry

  • Twelve years of age or older

  • Complete blood count (CBC), platelet, liver and kidney function within institutionalnormal 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 (seeinclusion criteria section) from the time of study enrollment through 6 months afterthe last dose of vorinostat and mirdametinib. Males with partners of childbearingpotential must use highly effective contraception from the time of study enrollmentthrough 3 months after the last dose of vorinostat.

  • Provides voluntary written consent prior to any study related activities, withparental/guardian consent and assent for those 12 to 17 years of age at enrollment.

Exclusion

Exclusion Criteria:

  • Pregnant or breastfeeding - females of childbearing potential must have a negativepregnancy test (serum or urine) within 7 days prior to the 1 st dose of the studydrugs.

  • Significant cardiac disease

  • Significant eye disease

  • Radiation therapy or chemotherapy in the past year.

Study Design

Total Participants: 8
Treatment Group(s): 1
Primary Treatment: mirdametinib and vorinostat
Phase: 1
Study Start date:
November 20, 2025
Estimated Completion Date:
January 01, 2027

Connect with a study center

  • University of Minnesota

    Minneapolis, Minnesota 55414
    United States

    Active - Recruiting

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