NCT06693284

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

Recruiting now EARLY_PHASE1 Last updated 3 February 2026

What this trial tests

EARLY_PHASE1 trial testing mirdametinib and vorinostat in Primary Malignant Peripheral Nerve Sheath Tumors in 8 participants. Currently enrolling.

Timeline

20 November 2025

Primary endpoint
1 January 2027

1 January 2027

Quick facts

Lead sponsor	University of Minnesota
Phase	EARLY_PHASE1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	20 November 2025
Primary completion	1 January 2027
Estimated completion	1 January 2027
Sites	1 location across United States

Drugs / interventions tested

• mirdametinib and vorinostat — full drug profile →

Conditions studied

• Primary Malignant Peripheral Nerve Sheath Tumors — all drugs for Primary Malignant Peripheral Nerve Sheath Tumors →

Sponsor

University of Minnesota

Who can join

12 and older, any sex, with Primary Malignant Peripheral Nerve Sheath Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own 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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Aberrant histone modifications in pediatric brain tumors.
   Hamanishi ET, Dang D, Venneti S. · · 2025 · cited 1× · PMID 40556679 · DOI 10.3389/fonc.2025.1587157
2. Sarcomas in Adolescents and Young Adults.
   Greenmyer JR, Allen-Rhoades W. · · 2026 · PMID 42159886 · DOI 10.1007/s11912-026-01781-8
3. Emerging Molecular Insights and Therapeutic Directions in Neurofibromatosis Type 1 and NF2-Related Schwannomatosis.
   Park S, Woo TG, Kang SM, Kim BH, et al · · 2026 · PMID 41898726 · DOI 10.3390/ijms27062867
4. Trametinib and Fimepinostat Induce Malignant Peripheral Nerve Sheath Tumor Cell Death In Vitro
   · 2026
5. Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.
   Zhu L, Jia X, Xu L, Chen L, et al · · 2026 · PMID 41541668 · DOI 10.1016/j.isci.2025.114429
6. Challenges and Progress for Treatment of Malignant Peripheral Nerve Sheath Tumors in the Context of Recent Successes for Sarcoma Therapy.
   Callaghan JF, Mattingly RR. · · 2025 · PMID 41374983 · DOI 10.3390/cancers17233781
7. Neurofibromatosis Type 1 and the Search for Effective Tumor Therapies Using High-Throughput Drug Screening.
   Bouley SJ, Housden BE, Walker JA. · · 2025 · PMID 41294711 · DOI 10.3390/curroncol32110649