Abemaciclib for Meningioma

Overseen By Ivy Research Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nader Sanai

Must not be taking: Coumarin anticoagulants

Disqualifiers: Cancer, Pregnancy, Liver disease, others

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: 1

Duration: 24 months

72 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use coumarin-derived anticoagulants. Other blood thinners like heparin are allowed.

What evidence supports the effectiveness of the drug Abemaciclib for treating meningioma?

Research suggests that CDK4/6 inhibitors, like Abemaciclib, may be effective for treating aggressive meningiomas, as these tumors often have issues with cell cycle regulation that these drugs target. While specific data on Abemaciclib for meningioma is limited, its mechanism of action shows promise based on preclinical evidence for similar drugs. ^{1 2 3 4 5}

How is the drug Abemaciclib unique for treating meningioma?

Abemaciclib is unique for treating meningioma because it is a selective inhibitor of CDK 4 and 6, which are proteins involved in cell cycle regulation. This mechanism targets a pathway often dysregulated in meningiomas, offering a novel approach compared to traditional surgery and radiation. ^{1 5 6 7 8}

What is the purpose of this trial?

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. Abemaciclib is a drug that is approved by the FDA, but not for brain tumors. Participants who consent to the trial will have surgical tissue collected from the planned surgical resection and tested. If the tissue shows positive results for RB cells and participants are qualified, they will be enrolled and receive study treatment two to five weeks after completing standard-of-care radiation therapy. This is a randomized clinical trial which means that participants will be randomly assigned to a treatment based on chance, like a flip of a coin. Neither the participant nor the researcher chooses the assigned group. Randomization will help the researchers study how the drug works by comparing the difference between the study drug and the placebo and how they work in treating brain tumors. This is a double-blinded study, which means that neither the participant nor the study team will know which treatment the participant is receiving.

Research Team

Nader Sanai, MD

Principal Investigator

Ivy Brain Tumor Center

Eligibility Criteria

Adults over 18 with newly-diagnosed grade 3 meningioma, who've completed radiation therapy and can swallow pills. They must use effective contraception if of childbearing potential and have good organ function. Excluded are those with other cancers, certain infections or severe medical conditions, pregnancy, known allergies to abemaciclib components, or prior CDK4/6 inhibitor treatment.

Inclusion Criteria

I can understand and am willing to sign the consent form myself or through a legal representative.

My cancer test shows positive for RB protein or no RB gene mutations.

I have recovered from my last radiation therapy, which was between 2 to 5 weeks ago.

Exclusion Criteria

You have had allergic reactions to any of the ingredients in abemaciclib.

I am currently using a coumarin-based blood thinner.

I haven't needed antibiotics or antivirals for an infection or high fever in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-5 weeks

1 visit (in-person)

Radiation

Participants receive standard-of-care radiation therapy

2-5 weeks

Treatment

Participants receive Abemaciclib or placebo twice daily on days 1-28 of each 28-day cycle

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 days after last study dose

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

24 months

Treatment Details

Interventions

• Abemaciclib
• Placebo

Trial Overview The trial is testing the effectiveness of abemaciclib versus a placebo in treating grade 3 meningioma after standard radiation therapy. It's randomized and double-blinded; neither participants nor researchers know who receives the actual drug or placebo.

Participant Groups

Group I: Active Treatment (Abemaciclib) Experimental Treatment 1 Intervention

Administered twice daily on days 1-28 of each 28-day cycle.

Group II: Placebo Placebo Group 1 Intervention

Administered twice daily on days 1-28 of each 28-day cycle.

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?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

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]

In a study involving 63 freshly operated meningiomas, the combination of the Pi3k inhibitor alpelisib and the MEK inhibitor trametinib showed a greater inhibitory effect on tumor cell viability and proliferation compared to everolimus, regardless of tumor grade or genomic status.

The combined treatment effectively reversed AKT activation induced by trametinib and provided an additive anti-proliferative effect, suggesting that co-targeting the Pi3k-AKT-mTOR and MAP kinase pathways could be a promising strategy for treating aggressive meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-Targeting MAP Kinase and Pi3K-Akt-mTOR Pathways in Meningioma: Preclinical Study of Alpelisib and Trametinib. Mondielli, G., Mougel, G., Darriet, F., et al.[2022]

Meningiomas, while mostly benign, can be aggressive and resistant to standard treatments like surgery and radiotherapy, highlighting the need for new therapeutic options.

CDK4/6 inhibitors show promise as a potential systemic treatment for high-grade meningiomas due to the common misactivation of the cell cycle in these tumors, with ongoing clinical trials aimed at optimizing their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK 4/6 inhibitors for the treatment of meningioma. Young, JS., Kidwell, RL., Zheng, A., et al.[2022]

In a phase 2 trial involving 25 patients with recurrent high-grade meningiomas, pembrolizumab (a PD-1 inhibitor) demonstrated promising efficacy, achieving a 6-month progression-free survival rate of 48% and a median progression-free survival of 7.6 months.

While 20% of patients experienced significant treatment-related adverse events (grade 3 or higher), the results indicate that pembrolizumab may be a viable treatment option for some patients with these aggressive tumors, warranting further investigation into the tumor microenvironment's role in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. Brastianos, PK., Kim, AE., Giobbie-Hurder, A., et al.[2022]

Meningiomas, which are benign tumors of the central nervous system, are influenced by steroid hormones, leading to high rates of relapse and challenges in complete surgical removal, especially when they affect vital structures.

Several clinical trials have tested various substances that interfere with steroid actions, such as RU486 and tamoxifen, showing potential for treating meningiomas and highlighting the need for further research into these therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endocrine treatment of meningiomas: a review]. da Motta, LA., da Motta, LD.[2019]

In a phase 1b study involving 50 patients with advanced non-small cell lung cancer (NSCLC), the combination of abemaciclib and pembrolizumab showed significant toxicity, with 80% of patients in cohort A and 76% in cohort B experiencing severe treatment-emergent adverse events.

Despite some antitumor activity, including a disease control rate of 56% in cohort A and 64% in cohort B, the overall risk-benefit profile of this combination therapy does not support further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. Pujol, JL., Vansteenkiste, J., Paz-Ares Rodríguez, L., et al.[2022]

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]

The combination of the CDK4/6 inhibitor palbociclib and radiation therapy significantly reduced tumor proliferation and size in pre-clinical models of anaplastic meningiomas and radiation-induced meningiomas, particularly in retinoblastoma-positive cells.

Palbociclib treatment led to a G1 cell cycle arrest and decreased expression of key cell cycle proteins without causing hepatic toxicity, suggesting it is a safe and effective therapeutic strategy for treating certain types of meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating anti-tumor activity of palbociclib plus radiation in anaplastic and radiation-induced meningiomas: pre-clinical investigations. Das, A., Alshareef, M., Martinez Santos, JL., et al.[2021]

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

Co-Targeting MAP Kinase and Pi3K-Akt-mTOR Pathways in Meningioma: Preclinical Study of Alpelisib and Trametinib. [2022]

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

CDK 4/6 inhibitors for the treatment of meningioma. [2022]

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

Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[Endocrine treatment of meningiomas: a review]. [2019]

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

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]

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

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

8. Italy pubmed.ncbi.nlm.nih.gov

Evaluating anti-tumor activity of palbociclib plus radiation in anaplastic and radiation-induced meningiomas: pre-clinical investigations. [2021]