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

Trial Summary

What is the purpose of this trial?

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

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.

What data supports the effectiveness of the drug Ulixertinib (BVD-523) for treating brain tumors?

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 low-grade gliomas, a type of brain tumor. ^{1 2 3 4 5}

What makes the drug Ulixertinib unique for treating brain tumors?

Ulixertinib is unique because it targets the ERK1/2 proteins in the MAPK pathway, which is often altered in brain tumors, offering a novel approach compared to other treatments that do not specifically inhibit this pathway. ^{1 4 5 6 7}

Research Team

Nazanin Majd

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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 meet the required imaging and surgical criteria.

Exclusion Criteria

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

I finished my radiotherapy less than 12 weeks ago.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

References

1. England 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. [2023]

2. United States 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Therapies in Rare Brain Tumours. [2021]

4. England 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. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid penetration of the colony-stimulating factor-1 receptor (CSF-1R) inhibitor, pexidartinib. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models. [2023]