Multiple Targeted Therapies for Meningioma

Recruiting at726 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: CYP3A4 inhibitors, CYP3A inducers

Disqualifiers: Uncontrolled hypertension, Diabetes, Hepatitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically strong inhibitors of CYP3A4, 14 days before joining the study if you have certain genetic mutations. If you are taking medications that affect CYP3A4 or CYP2D6, you may need to stop them, so it's important to discuss your current medications with the study team.

What data supports the effectiveness of the drugs Abemaciclib, Capivasertib, GSK2256098, and Vismodegib for treating meningioma?

While there is no direct evidence for these specific drugs in treating meningioma, research shows that targeted therapies focusing on pathways like Pi3K-Akt-mTOR and cell cycle regulation are being explored for aggressive meningiomas. Additionally, inhibitors of pathways like mTOR and FAK have shown some promise in clinical trials, suggesting potential for similar targeted drugs. ^{1 2 3 4 5}

How is the drug combination of Abemaciclib, Capivasertib, GSK2256098, and Vismodegib unique for treating meningioma?

This drug combination targets multiple pathways involved in tumor growth, such as the Pi3K-Akt-mTOR and MAP kinase pathways, and focuses on cell cycle regulation, which is different from traditional treatments that have shown limited effectiveness. It offers a novel approach by addressing various genetic mutations and signaling pathways specific to meningiomas, potentially providing a more personalized and effective treatment option. ^{1 2 3 5 6}

Research Team

Priscilla Brastianos, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

Inclusion Criteria

I have diabetes and specific genetic changes.

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

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

Exclusion Criteria

My high blood pressure is not under control.

I have not had major surgery in the last 28 days.

I am not on medications that affect certain genetic changes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment based on their mutation status: SMO inhibitor, FAK inhibitor, AKT inhibitor, or CDK inhibitor. Treatment cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for a maximum of 5 years from registration.

5 years

Treatment Details

Interventions

• Abemaciclib (Protein Kinase Inhibitor)
• Capivasertib (Protein Kinase Inhibitor)
• GSK2256098 (Protein Kinase Inhibitor)
• Vismodegib (Hedgehog Pathway Inhibitor)

Trial Overview 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.

Participant Groups

Group I: Arm D (abemaciclib) Experimental Treatment 1 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 Treatment 1 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 Treatment 1 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 Treatment 1 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)

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

Suzanne George

Alliance for Clinical Trials in Oncology

Chief Medical Officer since 2015

MD from Harvard Medical School

Evanthia Galanis

Alliance for Clinical Trials in Oncology

Chief Executive Officer since 2022

MD from Mayo Clinic

Brain Science Foundation

Collaborator

Trials

1

Recruited

120+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Apatinib, an antiangiogenic agent that inhibits VEGFR-2, showed promising results in three cases of recurrent anaplastic meningioma, with partial responses and progression-free survival times of 17.3, 10.3, and 14+ months.

The treatment was associated with manageable adverse events such as hypertension and hand-foot syndrome, suggesting that apatinib could be a viable option for patients with surgery and radiation-refractory anaplastic meningioma, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apatinib in recurrent anaplastic meningioma: a retrospective case series and systematic literature review. Wang, Y., Li, W., Jing, N., et al.[2021]

Meningiomas, particularly high-grade meningiomas (HGMs), are challenging to treat with traditional therapies, highlighting the need for novel approaches, especially since existing treatments have not shown significant clinical benefits.

Advancements in next-generation sequencing have revealed the genetic diversity of meningiomas, paving the way for personalized targeted therapies and new clinical trials that match patients with treatments based on their tumor's genetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Medical Treatments for Meningioma in the Molecular Era. Nigim, F., Wakimoto, H., Kasper, EM., et al.[2020]

Recent advances in understanding meningioma biology have identified new therapeutic targets, including the mTOR and Pi3K-Akt pathways, which are currently being explored in clinical trials for treating aggressive meningiomas.

Despite the discovery of potential targets and the use of therapies like Anti-VEGF and mTOR inhibitors, the treatment of high-grade meningiomas remains challenging, with limited efficacy from current options and a need for innovative approaches such as immunotherapy and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative treatments for meningiomas. Graillon, T., Tabouret, E., Salgues, B., et al.[2023]

In a study of 18 NF2 patients with progressive meningiomas, treatment with vistusertib, a dual mTORC1/mTORC2 inhibitor, resulted in stable disease in 94% of tumors, but only one tumor showed a partial response, indicating limited efficacy in significantly reducing tumor size.

The treatment was associated with high rates of severe side effects, leading to 78% of participants experiencing grade 3/4 adverse events and 9 participants discontinuing treatment, highlighting the need for improved tolerability in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective phase II trial of the dual mTORC1/2 inhibitor vistusertib for progressive or symptomatic meningiomas in persons with neurofibromatosis 2. Jordan, JT., Orr, CC., Thalheimer, RD., et al.[2023]

In the phase II CEVOREM trial involving 20 patients with recurrent aggressive meningiomas, the combination of everolimus and octreotide resulted in a 55% progression-free survival rate at 6 months, indicating significant efficacy for this treatment approach.

The treatment led to a major decrease in tumor growth rate, with 78% of tumors showing over a 50% reduction in growth at 3 months, suggesting that this combination therapy could effectively slow tumor progression in aggressive meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial. Graillon, T., Sanson, M., Campello, C., et al.[2021]

Meningiomas, the most common type of brain tumor, can often be cured through surgical removal, but those that are not completely removed or are more aggressive (WHO grade II and III) have a high chance of recurring.

While many drugs have been tested for treating recurrent meningiomas, most have shown little to no effectiveness; however, antiangiogenic drugs like bevacizumab, sunitinib, and vatalinib show promise and warrant further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiangiogenic treatment of meningiomas. Preusser, M., Marosi, C.[2020]

References

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

Apatinib in recurrent anaplastic meningioma: a retrospective case series and systematic literature review. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Emerging Medical Treatments for Meningioma in the Molecular Era. [2020]

3. France pubmed.ncbi.nlm.nih.gov

Innovative treatments for meningiomas. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Prospective phase II trial of the dual mTORC1/2 inhibitor vistusertib for progressive or symptomatic meningiomas in persons with neurofibromatosis 2. [2023]

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

Everolimus and Octreotide for Patients with Recurrent Meningioma: Results from the Phase II CEVOREM Trial. [2021]

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

Antiangiogenic treatment of meningiomas. [2020]