Cabozantinib for Meningioma

Recruiting at 3 trial locations

Overseen By Yazmin Odia, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Baptist Health South Florida

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Active malignancy, Uncontrolled hypertension, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 2 years

24 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. However, you cannot participate if you have taken certain cancer treatments or small molecule kinase inhibitors recently. Also, some blood thinners are not allowed, but others are permitted if you have been on a stable dose for at least a week.

What data supports the effectiveness of the drug Cabozantinib for treating meningioma?

Cabozantinib has shown significant responses in treating intracranial meningiomas in a patient with thyroid cancer, suggesting it might be a promising option for meningioma due to its action on VEGF receptors, which are involved in tumor growth. ^{1 2 3 4 5}

Is cabozantinib generally safe for humans?

Cabozantinib has been studied in people with liver and kidney cancers, showing some common side effects like tiredness, high blood pressure, and diarrhea. These side effects can often be managed with care and dose adjustments, and the treatment is generally considered safe with a low rate of stopping treatment due to side effects. ^{6 7 8 9 10}

How is the drug Cabozantinib unique for treating meningioma?

Cabozantinib is unique for treating meningioma because it is an oral drug that targets multiple pathways involved in tumor growth, specifically MET and VEGF receptor 2, which are not typically targeted by other treatments for this condition. This makes it a potential new option for patients with recurrent meningiomas, where surgery and radiation have limited effectiveness. ^{4 5 6 11 12}

What is the purpose of this trial?

A Phase II Study of Cabozantinib for Patients with Recurrent or Progressive Meningioma

Research Team

Yazmin Odia, MD

Principal Investigator

Miami Cancer Institute at Baptist Health, Inc.

Eligibility Criteria

This trial is for adults with recurrent or progressive meningioma who have tried standard treatments over 6 months ago or can't receive them. They must be in good physical condition, with proper liver, kidney, and blood function, not pregnant or breastfeeding, willing to use contraception and follow the study plan. People under 18, with certain heart issues, infections needing IV antibiotics, uncontrolled illnesses or recent serious injuries are excluded.

Inclusion Criteria

I am able to live my life with varying degrees of assistance.

Patients must have a detectable disease according to specific criteria.

Your blood clotting time is within a certain range based on the lab's normal results.

Exclusion Criteria

I do not have any major health issues that are not under control.

You are allergic to cabozantinib or any ingredients in it.

I haven't had any cancer treatment in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants self-administer cabozantinib 60 mg daily on a continuous 28-day schedule

2 years

Visits every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cabozantinib

Trial Overview The trial is testing Cabozantinib's effectiveness on patients with meningioma that has come back or gotten worse after treatment. It's a Phase II study where all participants will receive Cabozantinib to see how well it works against this type of brain tumor.

Participant Groups

Group I: Cabozantinib Experimental Treatment 1 Intervention

Participants will self-administer cabozantinib 60 mg at the same time daily by mouth on a continuous 28-day schedule. Participants will continue to take this medication as long as they are deriving benefit from it without significant treatment-related toxicities.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Baptist Health South Florida

Lead Sponsor

Trials

54

Recruited

8,100+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Findings from Research

In a trial involving 15 patients with recurrent or progressive meningiomas, the combination of hydroxyurea (HU) and imatinib showed a progression-free survival rate at 9 months of 0% for the combination group compared to 75% for the HU alone group, indicating that HU alone may be more effective in this context.

The study faced challenges with slow enrollment and was prematurely closed, making it difficult to draw definitive conclusions about the efficacy of the HU and imatinib combination, highlighting the need for further research to identify effective systemic therapies for meningiomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Mazza, E., Brandes, A., Zanon, S., et al.[2016]

In a study of 175 patients with meningiomas, key growth-promoting receptors such as IGF-1r, GHr, and EGFR E30 were found to be expressed in 88% to 94% of tumors, indicating potential targets for chemotherapy.

The study suggests that anti-progesterone and anti-angiogenic therapies could be effective for specific subsets of meningioma patients, particularly those expressing progesterone receptors or CD34, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An audit of immunohistochemical marker patterns in meningioma. Baxter, DS., Orrego, A., Rosenfeld, JV., et al.[2022]

Meningiomas, the most common type of brain tumor, often involve mutations in the NF2 gene in about 50% of patients, with other rare mutations linked to benign forms of the tumor.

Current treatments include surgical options and radiotherapy, while new therapies targeting the VEGF pathway and specific genetic mutations are being explored in clinical studies for aggressive cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical management challenges in meningioma. Mawrin, C., Chung, C., Preusser, M.[2021]

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]

Cabozantinib, an oral multitarget tyrosine kinase inhibitor, showed significant responses in treating recurrent meningiomas in a patient with concurrent thyroid carcinoma, suggesting its potential as a new therapeutic option.

This case report highlights the need for further prospective studies to evaluate cabozantinib's efficacy in meningiomas, especially given the limited effectiveness of current systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of Intracranial Meningiomas Following Treatment with Cabozantinib. Kotecha, R., Tonse, R., Appel, H., et al.[2021]

Cabozantinib is an effective treatment for advanced hepatocellular carcinoma (HCC) after failure of sorafenib, showing significant improvement in overall survival and progression-free survival compared to placebo in the phase 3 CELESTIAL trial.

Common side effects of cabozantinib include palmar-plantar erythrodysesthesia, hypertension, fatigue, and diarrhea, which are important to manage in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. Trojan, J.[2021]

Cabozantinib significantly improves progression-free survival (PFS) and overall survival (OS) in patients with advanced renal cell carcinoma (RCC) who have previously undergone antiangiogenic therapy, as demonstrated in the METEOR trial.

The drug also shows a higher objective response rate compared to everolimus, while maintaining a manageable safety profile, making it a valuable treatment option for advanced RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Review in Advanced Renal Cell Carcinoma. Al-Salama, ZT., Keating, GM.[2018]

Cabozantinib is an effective treatment for advanced hepatocellular carcinoma in patients previously treated with sorafenib, showing improved overall survival and progression-free survival compared to placebo in the phase III CELESTIAL study.

While cabozantinib can cause common adverse events like fatigue and gastrointestinal issues, these can be managed with supportive care and dose adjustments, allowing for continued treatment with a low rate of discontinuation due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma. Schwartz, G., Darling, JO., Mindo, M., et al.[2021]

Cabozantinib (Cabometyx) significantly improves progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC) compared to everolimus, with median PFS of 7.4 months versus 3.8 months, respectively, based on a study of 658 patients.

The treatment also shows a notable improvement in overall survival (OS), with median OS of 21.4 months for cabozantinib compared to 16.5 months for everolimus, indicating its efficacy as a second-line therapy after antiangiogenic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval: Cabozantinib for the Treatment of Advanced Renal Cell Carcinoma. Singh, H., Brave, M., Beaver, JA., et al.[2018]

Cabozantinib (Cabometyx®) is now approved as a first-line treatment for advanced renal cell carcinoma (RCC) in treatment-naïve adults, expanding its use beyond patients who have already received VEGF-targeted therapy.

In a phase 2 trial, cabozantinib significantly improved median progression-free survival and objective response rates compared to the standard treatment sunitinib, while its side effects are manageable, similar to other tyrosine kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. Lyseng-Williamson, KA.[2020]

Cabozantinib, a VEGF-tyrosine kinase inhibitor, has shown promising efficacy in a heavily pretreated metastatic renal cell carcinoma patient with brain metastases, achieving a complete response in the brain before radiation therapy.

This case highlights the potential intracranial activity of cabozantinib, which has been underreported in clinical trials, suggesting it may be a valuable treatment option for mRCC patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma. Uche, A., Sila, C., Tanoura, T., et al.[2020]

Cabozantinib is an effective receptor tyrosine kinase inhibitor that targets multiple pathways involved in tumor growth and metastasis, showing significant activity in various cancer types, including medullary thyroid cancer (MTC) and prostate cancer.

It gained FDA approval for first-line treatment of advanced MTC after demonstrating clinical benefit in trials, and ongoing phase III studies are investigating its efficacy in metastatic prostate cancer, where it has shown promising response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Grüllich, C.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). [2016]

2. Scotland pubmed.ncbi.nlm.nih.gov

An audit of immunohistochemical marker patterns in meningioma. [2022]

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

Biology and clinical management challenges in meningioma. [2021]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Regression of Intracranial Meningiomas Following Treatment with Cabozantinib. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Review in Advanced Renal Cell Carcinoma. [2018]

8. France pubmed.ncbi.nlm.nih.gov

Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma. [2021]

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

U.S. Food and Drug Administration Approval: Cabozantinib for the Treatment of Advanced Renal Cell Carcinoma. [2018]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. [2020]

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

Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma. [2020]

12. Germany pubmed.ncbi.nlm.nih.gov

Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. [2022]