What side effects are associated with this type of intervention?

Common treatments for glioblastoma, particularly kinase inhibitors like Defactinib (FAK/Pyk2 Inhibitor) and VS-6766 (Raf Inhibitor), are associated with several side effects. These include gastrointestinal symptoms (nausea, vomiting, diarrhea), fatigue, skin reactions (rash, hand-foot syndrome), hematologic abnormalities (anemia, thrombocytopenia), liver toxicity, and cardiovascular issues such as hypertension. These side effects are typical of kinase inhibitors used in cancer therapy.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for glioblastoma, focusing on inhibiting specific growth pathways. One notable example is Bevacizumab, an anti-VEGF monoclonal antibody that targets vascular endothelial growth factor to inhibit tumor blood vessel growth. While not a kinase inhibitor like Defactinib or VS-6766, it represents a targeted approach to glioblastoma treatment. Other kinase inhibitors, such as those targeting EGFR mutations, have also been explored, but specific approvals for FAK/Pyk2 or Raf inhibitors in glioblastoma are not well-documented.

What other types of research exist?

Promising novel alternatives for Glioblastoma treatment in 2024 include: 1) Bevacizumab, an anti-angiogenic therapy shown to be effective in various studies. 2) Everolimus, an mTORC1 inhibitor, which has shown potential in clinical trials. 3) Nivolumab, a PD-1 blockade immunotherapy, which has demonstrated activity in recurrent glioblastoma. These alternatives target different pathways and mechanisms, offering potential new avenues for treatment.

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Kinase Inhibitor

Avutometinib + Defactinib for Glioblastoma

Q: What is the mechanism of action of this treatment?

Glioblastoma treatments often target specific pathways that are crucial for tumor growth and survival. Defactinib, a FAK/Pyk2 inhibitor, works by inhibiting proteins that regulate tumor cell invasion and proliferation, which are often overexpressed in glioblastoma. VS-6766, a Raf inhibitor, targets the Raf/MEK/ERK pathway, which is frequently activated in glioblastoma cells, leading to uncontrolled cell division. By inhibiting these pathways, these treatments aim to reduce tumor growth and spread, offering potential benefits for glioblastoma patients by slowing disease progression and improving survival rates.

Phase < 1

Recruiting

Led By Jeffrey J Olson, MD

Research Sponsored by Emory University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at time of surgery

Awards & highlights

No Placebo-Only Group

Summary

This trial tests two new drugs, defactinib and VS-6766, for patients with glioblastoma, a type of aggressive brain tumor. These drugs aim to block specific proteins that help the tumor cells grow. The goal is to see how much of the drug reaches the brain and to check if it is safe.

Who is the study for?

Adults over 21 with new or recurrent glioblastoma who are undergoing surgery can join. They must be relatively healthy, with good organ function and blood counts, not have severe heart or lung conditions, no active hepatitis B/C or HIV, and agree to use effective contraception. Pregnant women, prisoners, those on certain drugs that interact with the trial medications, and minors are excluded.

What is being tested?

The trial is testing how much of two new drugs (Defactinib and VS-6766) gets into the brain and their safety in treating glioblastoma. These drugs target different growth pathways in tumor cells which may help stop tumor growth when used together.

What are the potential side effects?

Potential side effects include reactions related to kinase inhibitors such as fatigue, nausea, diarrhea; liver issues; changes in blood pressure; possible heart rhythm abnormalities; muscle pain or weakness could occur due to drug interactions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at time of surgery

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at time of surgery

This trial's timeline: 3 weeks for screening, Varies for treatment, and at time of surgery for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Concentration of avutometinib (VS-6766) that accumulates in the GBM and brain around tumor

Concentration of defactinib that accumulates in the glioblastoma (GBM) and brain around tumor

Incidence of adverse events associated with VS-6766

+1 more

Secondary study objectives

MEK and Erk in tumor, brain around tumor, and serum

Pyk2 and FAK phosphorylation in tumor, brain around tumor, and serum

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (Avutometinib)Experimental Treatment2 Interventions

Patients receive 1 dose of avutometinib PO while on study, prior to planned tumor resection. Patients undergo blood collection and donate resected tumor tissue while on study.

Group II: Arm I (Defactinib)Experimental Treatment2 Interventions

Patients receive 1 dose of defactinib PO while on study, prior to planned tumor resection. Patients undergo blood collection and donate resected tumor tissue while on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Defactinib

2013

Completed Phase 1

~60

Biospecimen Collection

2004

Completed Phase 3

~2030

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Glioblastoma treatments often target specific pathways that are crucial for tumor growth and survival. Defactinib, a FAK/Pyk2 inhibitor, works by inhibiting proteins that regulate tumor cell invasion and proliferation, which are often overexpressed in glioblastoma. VS-6766, a Raf inhibitor, targets the Raf/MEK/ERK pathway, which is frequently activated in glioblastoma cells, leading to uncontrolled cell division. By inhibiting these pathways, these treatments aim to reduce tumor growth and spread, offering potential benefits for glioblastoma patients by slowing disease progression and improving survival rates.