What side effects are associated with this type of intervention?

Common side effects of enzyme inhibitors used in treating meningiomas, such as Vismodegib, FAK inhibitor GSK2256098, Capivasertib, and Abemaciclib, include gastrointestinal issues (nausea, vomiting, diarrhea), fatigue, skin reactions (rash, dry skin), and hematologic abnormalities (anemia, leukopenia). Vismodegib may also cause muscle spasms and hair loss, while Abemaciclib can lead to liver enzyme abnormalities and an increased risk of infections.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for the treatment of meningioma using enzyme inhibitors like Vismodegib, FAK inhibitor GSK2256098, Capivasertib, and Abemaciclib. These drugs are currently being studied in clinical trials for their efficacy in treating progressive meningiomas. Broadly, treatment options for meningioma have included surgery, radiation therapy, and in some cases, chemotherapy, but targeted enzyme inhibition remains an investigational approach.

What other types of research exist?

Promising novel alternatives for meningioma treatment in 2024 include Bevacizumab, an anti-angiogenic agent, which has shown efficacy in reducing tumor growth and preserving hearing in NF2-related vestibular schwannomas. Additionally, Everolimus, an mTOR inhibitor, has demonstrated potential in treating progressive vestibular schwannomas in NF2 patients. These therapies offer different mechanisms of action compared to enzyme inhibitors and have shown promising results in clinical studies.

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Protein Kinase Inhibitor

Multiple Targeted Therapies for Meningioma

Phase 2

Recruiting

Research Sponsored by Alliance for Clinical Trials in Oncology

Eligibility Criteria Checklist

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

Must have

Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review

Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3, or CCNE1 copy number gain in tumor sample as documented specifically by the central laboratory, regardless of whether prior genotype testing outside of the central laboratory was performed

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies four drugs to treat patients with worsening meningioma. These drugs work by blocking enzymes that the tumor cells need to grow. The trial focuses on patients whose tumors have specific genetic mutations.

Who is the study for?

This trial is for adults with progressive meningiomas, including those with neurofibromatosis and stable CNS tumors. Participants can have had prior treatments and must have measurable disease growth documented by MRI or CT scans. Specific genetic alterations are required, and there's no limit on the number of previous therapies. Exclusions include uncontrolled gastric ulcers, allergies to similar drugs, certain medication restrictions based on genetics, recent major surgery, uncontrolled hypertension, and recent abdominal complications.

What is being tested?

The study tests how well four drugs—Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib—work in treating growing or worsening meningiomas. These drugs aim to halt tumor cell growth by blocking enzymes needed for cell proliferation.

What are the potential side effects?

Potential side effects may include digestive issues like ulcers or perforations (especially if pre-existing), allergic reactions to the drug components (for those with a history), blood sugar level changes requiring diabetic status considerations before joining the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My brain tumor has been confirmed as meningioma by a pathology review.

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My tumor has specific genetic changes identified by a central lab.

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My cancer is visible on scans and has grown or remained after surgery.

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My cancer has grown by 25% or more in less than 25 months.

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My meningioma has grown after radiation, and it's been weeks since my last treatment.

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My cancer can be seen and measured on a scan.

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I have received treatment before.

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I may or may not have had previous medical treatments.

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I have had multiple treatments for my condition.

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I haven't had chemotherapy or experimental treatments in the last 28 days.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression free survival (PFS)

Response rate defined as a confirmed complete response (CR) or partial response (PR)

Secondary study objectives

Incidence of adverse events according to National Cancer Institute CTCAE version 4.0

Overall survival (OS)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm D (abemaciclib)Experimental Treatment1 Intervention

Patients receive abemaciclib PO Q12H. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm C (capivasertib)Experimental Treatment1 Intervention

Patients receive capivasertib PO BID on days 1-4. Treatment repeats every 7 days for up to 1 cycle (28 days) in the absence of disease progression or unacceptable toxicity.

Group III: Arm B (FAK inhibitor GSK2256098)Experimental Treatment1 Intervention

Patients receive FAK inhibitor GSK2256098 PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL JULY 2017)

Group IV: Arm A (vismodegib)Experimental Treatment1 Intervention

Patients receive vismodegib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL FEBRUARY 2018)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Vismodegib

2015

Completed Phase 4

~1880

Capivasertib

2021

Completed Phase 1

~130

Abemaciclib

2019

Completed Phase 2

~1890

0 / 10Eligibility criteria met

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

The most common treatments for meningioma that involve enzyme inhibition work by targeting specific pathways crucial for tumor cell growth and survival. Vismodegib inhibits the Hedgehog signaling pathway, FAK inhibitors like GSK2256098 target focal adhesion kinase involved in cell adhesion and migration, Capivasertib inhibits the AKT pathway important for cell proliferation, and Abemaciclib inhibits cyclin-dependent kinases essential for cell cycle progression. These targeted approaches are significant for meningioma patients as they can effectively halt tumor growth and potentially reduce tumor size, improving disease management.