Multiple Targeted Therapies for Meningioma

Recruiting at 769 trial locations

Overseen By Tatjana Kolevska, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: CYP3A4 inhibitors, CYP3A inducers

Disqualifiers: Uncontrolled hypertension, Diabetes, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with worsening meningioma, a type of brain tumor. Researchers are studying drugs such as abemaciclib, capivasertib, and vismodegib to determine if they can block enzymes that promote tumor cell growth. The trial includes different groups to test each drug separately. It suits those with meningioma that has shown growth or has not improved after standard treatments. Participants must have a confirmed diagnosis of meningioma and evidence of tumor progression on medical images. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abemaciclib was safe in past studies. It is already approved for certain breast cancers and has benefited patients with specific brain tumors called meningiomas.

Capivasertib was also found to be safe. Common side effects, such as diarrhea and skin reactions, were reported but were manageable by adjusting the dose.

GSK2256098, another drug under testing, was well-tolerated in earlier studies, with some patients experiencing stable tumor growth.

Vismodegib is already used for treating basal-cell carcinoma, a type of skin cancer, and was found safe for those patients. However, it can cause serious birth defects, so it is not safe for pregnant women.

Overall, various studies suggest these drugs are generally well-tolerated, though side effects can occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for meningioma, which often involve surgical resection and radiation therapy, the investigational drugs in this trial offer targeted therapy options that aim to interfere with specific pathways in tumor cells. Abemaciclib is unique because it targets cyclin-dependent kinases (CDK 4/6), which play a crucial role in cell division, potentially slowing tumor growth. Capivasertib inhibits the AKT pathway, important in cell survival and proliferation, offering a different angle for disrupting tumor cell functions. GSK2256098 targets focal adhesion kinase (FAK), a protein involved in cell movement and survival, which could reduce tumor spread. Lastly, vismodegib blocks the Hedgehog signaling pathway, crucial for cell growth and differentiation, offering another novel approach. Researchers are excited because these drugs might provide more precise treatment options with potentially fewer side effects than traditional methods.

What evidence suggests that this trial's treatments could be effective for meningioma?

Research has identified several promising treatments for progressive meningioma, which are under study in this trial. Participants may receive Abemaciclib, which has been found to extend the time patients live without disease progression and may slow tumor growth. Another option is Capivasertib, which has helped some patients with recurring meningioma live longer, particularly those with specific genetic changes. GSK2256098, a type of FAK inhibitor, is also being studied; it has been well-tolerated and has helped patients with NF2-mutated meningiomas live longer without disease progression, suggesting it might slow the disease. Vismodegib, another treatment option, targets pathways that tumors use to grow and has shown effectiveness in certain tumors, indicating potential benefits for meningioma patients. Each treatment blocks enzymes crucial for tumor growth, offering hope for those facing this challenging condition. ^{1 2 4 6 7}

Who Is on the Research Team?

Priscilla Brastianos, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Capivasertib
• GSK2256098
• Vismodegib

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.

How Is the Trial Designed?

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)

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40842355/

Multicenter basket trial for Central Nervous System tumors ... Our data suggests that abemaciclib improves PFS and OS in patients with advanced meningioma. The 6-month PFS with abemaciclib in this study ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2001

Alliance A071401: Phase II trial of abemaciclib in patients ... The threshold for promising results for RR was 3+/24 pts. Results: Of 83 pts screened while the abemaciclib arm was open between September 15, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9354681/

CDK 4/6 inhibitors for the treatment of meningioma - PMC Outcomes data on ClinicalTrial ... The remaining two ongoing studies aim to examine the efficacy of twice daily dosing of oral Abemaciclib.

4. trials.braintumor.org trials.braintumor.org/trials/NCT05940493

Abemaciclib in Newly Diagnosed Meningioma Patients This study is being done to learn about how an investigational drug called abemaciclib works in treating patients with a newly-diagnosed grade 3 meningioma.

5. onclive.com onclive.com/view/dr-brastianos-looks-at-recent-data-in-high-grade-meningiomas

Dr. Brastianos on Recent Data in High-Grade Meningiomas In January 2023, Brastianos published grade II results from 36 patients with NF2 mutations assigned to GSK2256098. The FAK inhibitor induced a 6 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12202147/

Potential synergism of abemaciclib with chloroquine and ... A recently published phase II trial (Alliance A071401) using abemaciclib 200 mg twice per day showed safety, tolerability, and a 54% PFS at 6 months for Grade 2 ...

7. withpower.com withpower.com/trial/phase-2-meningioma-8-2023-c0d60

Abemaciclib for Meningioma Prior Safety DataThis treatment has passed at least one previous human trial. Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA ...