Ulixertinib for Brain Tumor

Overseen By Nazanin Majd, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Bevacizumab, Immunosuppressants, others

Disqualifiers: HIV, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ulixertinib (BVD-523) as a potential treatment for recurrent brain tumors, specifically to determine if it can cross the blood-brain barrier, the brain's protective shield. The focus is on two types of brain tumors: NF1-mutated low-grade glioma and CIC-mutated oligodendroglioma. Individuals who have experienced tumor regrowth after treatment for these tumors may be suitable candidates for this study. The goal is to determine if ulixertinib can effectively reach and impact these tumors. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that you cannot take certain prohibited medications. It's best to discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that ulixertinib is likely to be safe for humans?

Research has shown that ulixertinib, a drug targeting specific cell pathways, holds potential for treating brain tumors. Some patients with certain brain tumors experienced stable disease for several months while taking ulixertinib, suggesting the drug might help control tumor growth over time.

Regarding safety, current research lacks detailed information about side effects. As this trial is in an early phase, it primarily focuses on understanding the drug's safety and mechanism in the body. While ulixertinib is under study for its potential benefits, its safety in humans remains under careful monitoring and investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain tumors?

Unlike the standard treatments for brain tumors, which often involve surgery, radiation, or traditional chemotherapy, Ulixertinib is unique because it specifically targets the MAPK/ERK pathway, a key driver in certain tumor growths. This pathway-focused approach can potentially lead to more effective treatment with fewer side effects. Researchers are particularly excited about Ulixertinib for treating NF1-mutated low-grade gliomas and CIC-mutated oligodendrogliomas, as these genetic mutations can make tumors more susceptible to this kind of targeted therapy. By honing in on the cancer cells' specific vulnerabilities, Ulixertinib offers a promising, targeted treatment option that could transform care for these difficult-to-treat brain tumors.

What evidence suggests that ulixertinib might be an effective treatment for brain tumors?

Research shows that ulixertinib, a type of medicine, may help treat brain tumors, especially those linked to the MAPK pathway. This trial will study ulixertinib in two separate cohorts: one for patients with NF1-mutated low-grade glioma and another for those with CIC-mutated oligodendroglioma. Studies have shown that ulixertinib can pass through the blood-brain barrier, a protective shield around the brain, making it important for effective treatment. Early evidence suggests that ulixertinib might improve outcomes for patients with these tumors. While more research is needed, these findings offer hope for its effectiveness in treating certain brain tumors. ^{1 3 4 5 6}

Who Is on the Research Team?

Nazanin Majd

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with recurrent low-grade gliomas, a type of brain tumor, who've had prior treatments like radiation or chemotherapy can join. They must have proper organ function and be able to consent (or have a legal representative consent). Pregnant women and those with certain infections or conditions that could interfere with the study are excluded.

Inclusion Criteria

I agree to use effective birth control during and for 3 months after the study.

I agree to use contraception during and for 3 months after the study.

I have received specific treatments.

Exclusion Criteria

I finished my radiotherapy less than 12 weeks ago.

Patient currently participating in a study of an investigational agent or using an investigational device for therapeutic purposes.

I have not been treated with bevacizumab in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ulixertinib to evaluate its ability to penetrate the blood-brain barrier and assess anti-tumor activity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and response rates

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ulixertinib

Trial Overview The trial is testing Ulixertinib's ability to cross the blood-brain barrier in patients with recurring brain tumors. It involves adults who meet specific surgical criteria and have confirmed diagnoses based on histological and molecular standards.

How Is the Trial Designed?

Group I: Cohort 2: CIC-mutated oligodendroglioma Experimental Treatment 1 Intervention

Group II: Cohort 1: NF1-muated low-grade glioma Experimental Treatment 1 Intervention

Ulixertinib is already approved in United States for the following indications:

Approved in United States as Ulixertinib for:

• None (investigational)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

BioMed Valley Discoveries, Inc

Industry Sponsor

Trials

19

Recruited

650+

Published Research Related to This Trial

Ulixertinib, an ERK1/2 inhibitor, effectively inhibited the MAPK pathway and reduced cell viability in pediatric low-grade glioma (pLGG) models, showing promise for treating these tumors.

In preclinical studies, ulixertinib demonstrated significant tumor growth inhibition and increased survival in mice, supporting its potential for clinical evaluation as a monotherapy and in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first-in-class ERK inhibitor ulixertinib shows promising activity in mitogen-activated protein kinase (MAPK)-driven pediatric low-grade glioma models. Sigaud, R., Rösch, L., Gatzweiler, C., et al.[2023]

Recent advancements in molecular techniques have identified actionable alterations in rare CNS tumors, leading to potential targeted therapies that can improve neurological symptoms and quality of life.

Specific treatments targeting pathways like mTOR in SEGAs and BRAF V600E mutations in certain glial and glioneuronal tumors show promise, highlighting the importance of personalized medicine in managing these challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapies in Rare Brain Tumours. Bruno, F., Pellerino, A., Bertero, L., et al.[2021]

In a study involving 158 patients with glioblastoma, the combination of galunisertib and lomustine did not show improved overall survival compared to lomustine alone, with median overall survival times being similar across all treatment groups.

Patients receiving galunisertib alone experienced fewer severe drug-related side effects compared to those treated with lomustine, suggesting a potentially safer profile for galunisertib as a monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II randomized study of galunisertib monotherapy or galunisertib plus lomustine compared with lomustine monotherapy in patients with recurrent glioblastoma. Brandes, AA., Carpentier, AF., Kesari, S., et al.[2020]

Pexidartinib, a CSF-1R inhibitor, was well-tolerated in a study involving five male rhesus macaques, with no severe toxicities observed, indicating a favorable safety profile for potential CNS tumor treatment.

The study found that pexidartinib had limited penetration into the cerebrospinal fluid (CSF) after a single oral dose, suggesting that while it is safe, its effectiveness in treating CNS tumors may be compromised due to poor CNS availability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib. Shankarappa, PS., Peer, CJ., Odabas, A., et al.[2021]

In a study of 10 patients with recurrent malignant glioma, the combination of apatinib and irinotecan resulted in a 55% objective response rate and a 78% disease control rate, indicating promising efficacy for this treatment approach.

The treatment was generally well-tolerated, with the most common side effects being gastrointestinal reactions, hypertension, and myelosuppression, suggesting that while there are some risks, the safety profile is manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. Wang, L., Liang, L., Yang, T., et al.[2022]

Erlotinib and gefitinib did not significantly inhibit EGFR activity in recurrent or progressive malignant gliomas, suggesting limited efficacy of these drugs in this context.

The study identified novel genomic changes, including deletions on chromosomes 6, 21, and 22, which could serve as new targets for future research, indicating that the mechanisms of drug sensitivity may differ between brain and lung tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Lassman, AB., Rossi, MR., Raizer, JJ., et al.[2022]

In pediatric brain tumor models with BRAFV600E mutations, trametinib effectively induces tumor regression by inhibiting both MAPK and TORC1 signaling pathways, demonstrating its potential as a treatment option.

The study found that resistance to trametinib developed quickly in these tumors, but combining trametinib with rapamycin helped prevent or slow down this resistance, suggesting a promising strategy for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models. Li, F., Bondra, KM., Ghilu, S., et al.[2023]

Citations

1. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii106/7890523

CTNI-46. WINDOW-OF-OPPORTUNITY TRIAL OF ... We hypothesized that ulixertinib crosses the blood-brain barrier (BBB) and it will result in improved responses in MAPK-activated lower-grade gliomas in adults.

2. withpower.com withpower.com/trial/ulixertinib-for-brain-tumor-f44b0

Ulixertinib for Brain Tumor Ulixertinib has shown promising responses in adult patients with solid tumors driven by the MAPK pathway, which is similar to the pathway involved in pediatric ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10013652/

The first-in-class ERK inhibitor ulixertinib shows promising ... These data indicate a high clinical potential of ulixertinib for the treatment of pLGG and strongly support its first clinical evaluation in pLGG as single ...

4. biomed-valley.com biomed-valley.com/wp-content/uploads/2024/12/SNO2024ulixertinibposter110124.pdf

Window-of-Opportunity Trial of Ulixertinib for MAPK- ... We hypothesized that ulixertinib crosses the intact blood- brain barrier (BBB) and it will result in improved responses in MAPK-activated gliomas. • The trial ...

5. cancer.gov cancer.gov/clinicaltrials/NCI-2023-02713

Ulixertinib for the Treatment of Recurrent Mitogen-Activated ... Giving ulixertinib may kill more tumor cells and improve control of the disease in patients with recurrent MAPK-activated gliomas. Eligibility Criteria ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05804227?term=ULIXERTINIB&rank=7

Window-of-Opportunity Trial of Ulixertinib for MAPK ... Primary Objective: 1. To evaluate the ability of ulixertinib to penetrate the BBB in patients with recurrent MAPK-activated LGG (ulixertinib tumor ...