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SJ901: Study of Mirdametinib as a Treatment for Children, Adolescents and Young Adults with Low-Grade Glioma

Phase 1/2 Evaluation of Mirdametinib, a Brain-Penetrant MEK 1/2 Inhibitor, for Children, Adolescents and Young Adults with Low-Grade Glioma

Categories:

Brain Tumor

Phase I/II

Diseases Treated:

Low-Grade Glioma

Eligibility Overview:

At least 2 years old and younger than 25 years old

Diagnosis of progressive or relapsed low-grade glioma 

  1. SJ901 is a multi-arm, phase 1/2 dose-escalation/dose-finding and early efficacy study of the brain-penetrant inhibitor, mirdametinib in patients with pediatric low-grade glioma (pLGG).

    Mirdametinib is a highly selective non-ATP competitive inhibitor of MEK1 and MEK2 that has been shown to inhibit the phosphorylation of the MAPK substrates ERK1 and ERK2, leading to impaired tumor cell growth in laboratory studies.

    Phase 1 of this trial will evaluate the safety, tolerability and pharmacokinetics of mirdametinib when dosed continuously in patients with progressive or relapsed low-grade glioma. Phase 2 is designed to estimate the objective response rate and duration of response to mirdametinib in pLGG. Patients enrolled in Phase 2 will be stratified into one of three treatment cohorts based on tumor status and history of MEK inhibitor exposure. 

    Primary Objectives:

    • Determine the safety and tolerability and estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of mirdametinib dosed twice daily in pediatric patients with progressive or recurrent low-grade glioma
    • To evaluate the effectiveness of mirdametinib in patients with recurrent and/or progressive WHO grade I or grade II glioma not previously treated with MEK inhibitors
    •  To describe the pharmacokinetics of mirdametinib in pediatric patients

    Eligibility Criteria

    Inclusion criteria include:

    •  At least 2 years old and younger than 25 years old
    • Confirmed diagnosis of primary or relapsed tumor, including:
      • Low-grade glioma/astrocytic tumor/glioneuronal tumor/neuroepithelial tumor
      • Pilocytic astrocytoma
      • Pilomyxoid astrocytoma
      • Pleomorphic xanthroastrocytoma
      • Ganglioglioma
      • Gangliocytoma
      • Diffuse glioma, diffuse astrocytoma, oligodendroglioma, or oligoastrocytoma
      • Papillary glioneuronal tumor
      • Rosette-forming glioneuronal tumor
      • Diffuse leptomeningeal glioneuronal tumor
      • Central neurocytoma, extraventricular neurocytoma
      • Angiocentric glioma
      • Dysembryoplastic neuroepithelial tumor (DNET), septal DNET, myxoid glioneuronal tumor
      • Tectal glioma
      • Desmoplastic infantile astrocytoma / ganglioglioma
      • Polymorphous low-grade neuroepithelial tumor of the young
      • Multinodular and vacuolating neuronal tumor
    • Tumor must show evidence supporting MAPK pathway activation as defined by IHC, FISH and/or DNA/RNA sequencing or occur in a participant with known NF1, NF2, SOS1, RAF1, or PTPN11 germline mutation.

    Exclusion Criteria include:

    •  One of the following tumors:
      • High-grade (WHO III or IV)
      • Subependymal giant cell astrocytoma
      • Ependymoma
      • Histone H3 K27M/K28M or G34/G35-mutant
      • BRAF V600 mutant
      • NTRK1/2/3, ALK, or ROS1 fusion-positive
      • IDH 1/2 mutant
    • Currently receiving other anticancer or investigational agents or recovering from toxicity related to the agent
    • Central serous retinopathy
    • Retinal vein occlusion or retinal detachment
    • Uncontrolled glaucoma
    • History of clinically significant interstitial lung disease
    • History of asthma, reactive airway disease or viral pneumonitis that is not resolved or well-controlled.

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in the U.S.

  2. Pediatric low-grade glioma tumors are the most common central nervous system tumor in children. Treatments typically include surgery, observation, chemotherapy (anti-cancer medicine) or radiation. If the tumor is in an area where it is safe to remove, the neurosurgeon will attempt to remove as much as possible.

    SJ901 is a study of an experimental drug called mirdametinib. It is experimental because it has not been approved by the U.S. Food and Drug Administration. Mirdametinib belongs to a class of drugs called MEK inhibitors. It has been used in children and adults, but there is a lot we do not know about it yet.  We are using mirdametinib because it is in a drug class that seems to be effective in treating low-grade glioma. It is also available in a liquid form, which allows patients who cannot swallow to take the drug.

    This study will be done in two parts, or phases. Phase 1 will determine the highest dose of mirdametinib that can be taken safely. During this phase, we will also look to see how well the drug is working in young patients. Phase 2 will see how well tumors respond to the drug.

    You may or may not benefit from taking part in this study. However, information learned from this study may help future patients with low-grade glioma tumors.

    Purpose of this clinical trial

    The main goal of this study is to test the experimental drug mirdametinib in hopes of finding a treatment that may be effective against low-grade glioma brain tumors in children, adolescents and young adults.

    Eligibility overview

    • At least 2 years old and younger than 25 years old
    • Diagnosis of progressive or relapsed low-grade glioma 
  3. SJ901
    Sponsors: St. Jude Children’s Research Hospital
    ClinicalTrials.gov identifier NCT04923126
    Trial Start Date: June 2021
    Estimated Enrollment: 132
    Study Type: Interventional
    Study Phase: Phase 1/2  
    Conditions: Low-grade glioma
    Ages: 2 to 24 years old
    Principal investigator: Giles Robinson, MD
    Anna Vinitsky, MD, MS
    Study Sites: St. Jude Children’s Research Hospital 
    For a consultation or to discuss SJ901: St. Jude Brain Tumor Program
     1-800-349-4334 or 901-595-2544
    braintumors@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: 901-595-2544
Fax: 901-595-6211

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.