GliomasEarly Phase 1NCT05804227
Window-of-Opportunity Trial of Ulixertinib for MAPK-Activated Gliomas
A Early Phase 1 study testing Ulixertinib in people with Gliomas, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To learn if the study drug, ulixertinib, can cross over the blood-brain barrier in patients with recurrent brain tumors Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gliomas
- What is being tested?
- Ulixertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Apr 2023to 22 Sep 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- We will not select for CIC mutation in oligodendrogliomas in the surgical cohort as an inclusion criteria but will check CIC mutation status on the recurrent tissue for two main reasons; 1-CIC mutation is particularly enriched in recurrent OD (Barthel, Johnson et al. 2019) and not newly diagnosed disease, 2- Recurrence happens after more than 10 years and even longer in patients previously treated with radiation and chemotherapy (Bell, Zhang et al. 2020), therefore confirmation of CIC mutation based on archival tissue at the time of diagnosis is very challenging.
- Mutational status requires a pathology report, genomic sequencing, or immunohistochemical report of a mutation or activation of the RAS/RAF/MEK/ERK pathway.
Show all 34Show fewer
- 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.
- Demonstrate adequate organ function as defined in the Table below. All screening labs should be performed within 14 days (+3 working days) of treatment initiation.
- Organ System - Laboratory Value
- Hematological Absolute neutrophil count (ANC) ≥ 1,500 /mcL
- Platelets ≥ 100,000 /mcL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
- Renal
- Serum creatinine OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR
- ≥ 50 mL/min for patient with creatinine levels > 1.5 X institutional ULN
- Cardiac
- LVEF ≥ 50%
- Hepatic
- Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN
- AST (SGOT) and ALT (SGPT) ≤ 3.0 X ULN
- Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN
- Creatinine clearance should be calculated per institutional standard.
- Female patients of childbearing potential should have a negative serum pregnancy test within 14 days (+ 3 working days) of study enrollment.
- Male and female patients of childbearing potential agree to use highly effective contraception throughout the study and at least 90 days after the last study treatment administration.
- Male patients should agree to use an adequate method of contraception during the course of the study and for 90 days after the last dose of the study drug.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
- Is taking prohibited concomitant medications (Appendix 5) and is unable to discontinue these medications prior to study enrollment.
- A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Nazanin Majd, MD, 713-792-4515, nkmajd@mdanderson.org
Nazanin Majd, MD
About this study
To learn if the study drug, ulixertinib, can cross over the blood-brain barrier in patients with recurrent brain tumors
Read the detailed description
Primary Objective:
- Surgical: To evaluate the ability of ulixertinib to penetrate the BBB in patients with recurrent MAPK-activated gliomas (ulixertinib tumor concentration, tumor/plasma ratio)
- Non-surgical: To assess anti-tumor activity of ulixertinib for patients with recurrent MAPK-activated gliomas (objective response rate (ORR))
Secondary Objectives:
- To assess anti-tumor activity of ulixertinib for patients with recurrent MAPK-activated gliomas
- Progression-free-survival (PFS)
- Overall survival (OS)
- Disease control rate (DCR)
- Duration of response (DOR)
- Time to response (TTR)
- Time to next intervention
- To assess safety and tolerability of ulixertinib in MAPK-activated gliomas
- To evaluate the ability of ulixertinib to reach cerebrospinal fluid (ulixertinib CSF concentration, tumor/CSF ratio)
- Conditions
- Gliomas
- Being tested
- Ulixertinib
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UlixertinibDrug
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).
UlixertinibDrug
Non-Surgical:
Patients (12 years and above) with MAPK-activated gliomas will receive Ulixertinib by mouth twice a day continuously on a daily basis for cycles of 28 day.
| Study group | Role | What they receive |
|---|---|---|
| Surgical | Experimental | Not described Receives: Drug: Ulixertinib |
| Non-Surgical | Experimental | Not described Receives: Drug: Ulixertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2023
- Study start20 Apr 2023
- Primary completion22 Sep 2027 (estimated)
- Study completion22 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomasStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Responsible party
- Sponsor
- Investigators
- Nazanin Majd, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05804227
- Sponsor's protocol ID
- 2022-0585
- Other IDs
- NCI-2023-02713
- Status last verified
- Oct 2026
- First submitted
- 27 Mar 2023
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Window-of-Opportunity Trial of Ulixertinib for MAPK-Activated Gliomas
- ClinicalTrials.gov ID
- NCT05804227
- Acronym / sponsor ID
- 2022-0585
- Conditions
- Gliomas
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Study start
- 20 Apr 2023 (actual)
- Primary completion
- 22 Sep 2027 (estimated)
- Study completion
- 22 Sep 2027 (estimated)
- First posted
- 7 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To learn if the study drug, ulixertinib, can cross over the blood-brain barrier in patients with recurrent brain tumors
Detailed description
Primary Objective:
- Surgical: To evaluate the ability of ulixertinib to penetrate the BBB in patients with recurrent MAPK-activated gliomas (ulixertinib tumor concentration, tumor/plasma ratio)
- Non-surgical: To assess anti-tumor activity of ulixertinib for patients with recurrent MAPK-activated gliomas (objective response rate (ORR))
Secondary Objectives:
- To assess anti-tumor activity of ulixertinib for patients with recurrent MAPK-activated gliomas
- Progression-free-survival (PFS)
- Overall survival (OS)
- Disease control rate (DCR)
- Duration of response (DOR)
- Time to response (TTR)
- Time to next intervention
- To assess safety and tolerability of ulixertinib in MAPK-activated gliomas
- To evaluate the ability of ulixertinib to reach cerebrospinal fluid (ulixertinib CSF concentration, tumor/CSF ratio)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Surgical | Experimental | Drug: Ulixertinib |
| Non-Surgical | Experimental | Drug: Ulixertinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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.
- We will not select for CIC mutation in oligodendrogliomas in the surgical cohort as an inclusion criteria but will check CIC mutation status on the recurrent tissue for two main reasons; 1-CIC mutation is particularly enriched in recurrent OD (Barthel, Johnson et al. 2019) and not newly diagnosed disease, 2- Recurrence happens after more than 10 years and even longer in patients previously treated with radiation and chemotherapy (Bell, Zhang et al. 2020), therefore confirmation of CIC mutation based on archival tissue at the time of diagnosis is very challenging.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UlixertinibSurgical: 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). | Drug | Non-Surgical, Surgical |
| UlixertinibNon-Surgical: Patients (12 years and above) with MAPK-activated gliomas will receive Ulixertinib by mouth twice a day continuously on a daily basis for cycles of 28 day. | Drug | Non-Surgical, Surgical |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion; an average of 1 year.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
Related trials for Gliomas
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nazanin Majd, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ulixertinib in people with Gliomas, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nazanin Majd, MD ((713) 792-4515, nkmajd@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026; AzTrials last refreshed its copy on 8 Nov 2026.