Window-of-Opportunity Trial of Ulixertinib for MAPK-Activated Gliomas

NCT05804227 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0585NCI-2023-02713
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if the study drug, ulixertinib, can cross over the blood-brain barrier in patients with recurrent brain tumors

Conditions

Gliomas

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (2)

Surgical

EXPERIMENTAL

Drug: Ulixertinib

Non-Surgical

EXPERIMENTAL

Drug: Ulixertinib

Interventions

Ulixertinib DRUG

Surgical: Only adults with recurrent MAPK-activated gliomas will be accrued to the surgical cohort. Patients will receive Ulixertinib by mouth twice a day for two weeks and will undergo tumor resection subsequently on day 14 (+/- 3 working days).

Non-Surgical; Surgical

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial (by participant or legally authorized representative), and assent when applicable. Participants with cognitive impairment will be enrolled. Cognitive function will be assessed by the treating physician or designee through a neurological examination. The formal consent for such participants will be obtained from their legally authorized representative.
• Surgical: Be 18 years of age or older on day of signing informed consent. Non-surgical: Be 12 years of age or older on day of signing informed consent.
• \*Pediatric patients will be dosed at the RP2D of 260mg/m2 EVERY 12 HRS continuously for 28-day cycles. The pediatric maximal single dose is 450mg. Since the smallest tablet strength of ulixertinib is 150mg, dosing in subjects with a BSA \< 0.9m2 will be inaccurate. Therefore, only subjects with a BSA of ≥ 0.9m2 are eligible.
• MAPK-activated gliomas, mixed glioma or glioneural tumors, including but not limited to those with mutations in BRAF, FGFR, PTPN11, somatic NF-1, NF-1 syndrome-associated gliomas, and recurrent oligodendrogliomas, CIC mutated. Somatic-only NF-1-mutated grade 3, 4 astroctyoma will not be included.
• Mutational status requires a pathology report, genomic sequencing, or immunohistochemical report of a mutation or activation of the RAS/RAF/MEK/ERK pathway.
• Prior resection or biopsy with confirmed diagnosis of glioma. Low grade gliomas patients (grade 1, 2) and oligodendroglioma (grade 2, 3) must have had prior radiation OR chemotherapy for the treatment of glioma. High grade glioma patients (grades 3 and 4 excluding oligodendroglioma) must have had prior radiation.
• Have the following imaging and surgical criteria:
• Surgical: Progressive disease per RANO low-grade glioma or high-grade glioma criteria depending on tumor grade AND presence of respectable tumor are required.
• Non-surgical: Progressive disease per RANO low-grade glioma or high-grade glioma criteria depending on tumor grade.
• Patients having undergone radiation are eligible as long as they are at least 12 weeks from radiation with evidence of disease progression per advanced brain tumor imaging \[(ABTI); includes spectroscopy and perfusion MR studies\] or biopsy.
• Any number of prior relapses.
• Be willing to provide tissue from an archival tissue sample.
• Presence of archival tissue sample of at least 1 H\&E and 10 unstained slides. One tissue block will be requested but 10 unstained slides are acceptable if tissue block is not available.
• Have a performance status of ≥ 60 on the KPS.
• If patient is on steroids, patient must be on a stable or decreasing dose of steroids one week prior to screening MRI. Patients cannot be on more than 16mg of dexamethasone or equivalent per day.

You may not qualify if:

• Treatment with bevacizumab less than 3 months prior to enrollment.
• Presence of implanted chemotherapy. Previously resected implanted chemotherapy is not excluded.
• Less than 12 weeks from completing radiotherapy. Patients with proven progressive disease by biopsy or partial resection or with new lesions outside of the radiation field should not be excluded even if they are within 12 weeks of radiation.
• Patient currently participating in a study of an investigational agent or using an investigational device for therapeutic purposes.
• Patient has a diagnosis of severe immunodeficiency or is receiving systemic immunosuppressive therapy (except for steroids) within 7 days of study entrance.
• Patient has had prior chemotherapy or targeted small molecule therapy, within 3 weeks prior to study Day 1, or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If patient received major surgery (other than craniotomy), they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit.
• Has contraindication for undergoing MRIs.
• Is not a candidate for non-emergent surgical resection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• BioMed Valley Discoveries, Inc: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Glioma

Interventions

ulixertinib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Nazanin Majd, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nazanin Majd, MD

CONTACT

(713) 792-4515; nkmajd@mdanderson.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2023
• First Posted: April 7, 2023
• Study Start: April 20, 2023
• Primary Completion (Estimated): September 22, 2027
• Study Completion (Estimated): September 22, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)