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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cabozantinib (Cabometyx) to determine its effectiveness in treating recurrent or worsening meningioma, a type of brain tumor. The goal is to assess how well cabozantinib slows the disease. Suitable candidates for this trial include individuals with a meningioma diagnosis whose condition has returned or progressed after treatments such as surgery or radiation. As a Phase 2 trial, the research focuses on evaluating the treatment's efficacy in a smaller group, providing an opportunity to contribute to significant findings.

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.

Is there any evidence suggesting that cabozantinib is likely to be safe for humans?

Research has shown that the FDA has already approved cabozantinib for treating other types of cancer, indicating it has passed safety checks for those uses. In a study involving people with meningiomas (a type of brain tumor), researchers are carefully monitoring cabozantinib for safety. Other studies have consistently shown a stable safety record, with no new safety issues emerging. However, like all treatments, it can cause side effects. Discussing these potential effects with the medical team is important before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for meningioma?

Cabozantinib is unique because it targets meningioma differently than standard treatments like surgery and radiation. While most treatments focus on physically removing or destroying the tumor, cabozantinib is a targeted therapy that works by inhibiting specific proteins involved in tumor growth and blood vessel formation, potentially slowing the progression of the disease. Researchers are excited about cabozantinib because it offers a less invasive option that patients can take orally, and it may provide benefits even when other treatments have failed.

What evidence suggests that cabozantinib might be an effective treatment for meningioma?

Research shows that cabozantinib, which participants in this trial will receive, might help treat meningioma, a type of brain tumor. Studies have found that cabozantinib can block certain proteins that aid tumor growth, potentially slowing or stopping their development. In some patients with brain meningiomas, cabozantinib led to significant tumor shrinkage. Positive results have also been reported in other types of tumors, suggesting its potential effectiveness. ^{1 3 4 6 7}

Who Is on the Research Team?

Yazmin Odia, MD

Principal Investigator

Miami Cancer Institute at Baptist Health, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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 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]

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]

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 (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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8167720/

Regression of Intracranial Meningiomas Following Treatment ... A phase II trial examined the efficacy and safety of cabozantinib in 222 patients with progressive or recurrent GBM, and initial results ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05425004?term=ANHYDROUS%20LACTOSE&rank=6

Study Details | NCT05425004 | Cabozantinib for Patients ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33919580/

Regression of Intracranial Meningiomas Following Treatment ... In this case report, we provide data regarding significant responses in two radiographically diagnosed intracranial meningiomas in a patient with concurrent ...

4. mskcc.org mskcc.org/cancer-care/clinical-trials/24-325

A Phase 2 Study of Cabozantinib in People With Meningioma By blocking these enzymes, cabozantinib may help slow or stop the growth of your cancer. This drug is taken orally (by mouth).

5. researchgate.net researchgate.net/publication/371876182_A_Review_of_Recurrent_Meningiomas_with_Prolonged_Response_to_Cabozantinib_an_Oral_Multitarget_Tyrosine_Kinase_Inhibitor

(PDF) A Review of Recurrent Meningiomas with Prolonged ... Conclusion The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-cabozantinib-adults-and-pediatric-patients-12-years-age-and-older-pnet-and-epnet

FDA approves cabozantinib for pNET and epNET OS data were not mature with 83 (63% of patients enrolled) deaths in the cabozantinib arm and 40 (60% of patients enrolled) in the placebo arm ( ...

7. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-us-fda-approval-cabometyxr-cabozantinib-4

Exelixis Announces U.S. FDA Approval of CABOMETYX ... The safety profile of CABOMETYX observed in each CABINET cohort was consistent with its known safety profile. No new safety signals were ...