Cabozantinib for Childhood Cancer

Recruiting at 7 trial locations

Overseen By Parth Patel, MPH, CCRP

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Anticancer agents, Anticonvulsants

Disqualifiers: Major surgery, Myocardial infarction, 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: Unknown

Duration: 12 months

86 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of cabozantinib in treating various pediatric cancers, particularly those with limited treatment options and a tendency to return after treatment. Cabozantinib targets specific proteins involved in cancer growth. The study is expanding to include a wider range of tumors, such as neuroblastomas and other high-risk solid tumors. It suits children and young adults who have undergone previous cancer treatments but still have residual disease or are at high risk for recurrence. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications before enrolling. Specifically, you must not have received myelosuppressive chemotherapy within 3 weeks, non-myelosuppressive anticancer agents within 14 days, biological anticancer therapy within 21 days, and certain types of radiation therapy within specified timeframes before enrollment.

Is there any evidence suggesting that cabozantinib is likely to be safe for children with cancer?

Research has shown that cabozantinib has been studied in various cancers, including kidney cancer, and is generally well-tolerated. Studies like CABOSUN and METEOR did not identify any new safety issues with cabozantinib. Common lab tests revealed abnormalities in more than 25% of patients, but these were typical and expected.

For children and teens, the safety of cabozantinib remains under investigation. It has been approved for some younger patients with thyroid cancer, suggesting some safety evidence for its use in children. However, more research is needed to confirm its safety for other cancer types in this age group.

In summary, while cabozantinib has shown a manageable safety profile in adults, its effects in children are still being explored. This trial aims to gather more information on its safety for young patients with different types of cancer. ^{1 2 3 4 5}

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

Cabozantinib is unique because it targets cancer cells differently from standard treatments for childhood cancer. Most traditional therapies work by targeting rapidly dividing cells indiscriminately, which can affect both cancerous and healthy cells. However, cabozantinib specifically inhibits certain proteins that are essential for cancer cell growth and survival, making it potentially more effective and less harmful to healthy cells. Additionally, its tablet formulation allows for easier administration compared to some intravenous treatments, which can be more invasive and less convenient for young patients. Researchers are excited about cabozantinib because it offers a promising new approach with the potential for improved outcomes in treating childhood cancer.

What evidence suggests that cabozantinib might be an effective treatment for pediatric solid tumors?

Research has shown that cabozantinib, the treatment under study in this trial, has potential in treating various solid tumors in children. An earlier study found that cabozantinib helped shrink tumors in four patients and maintained disease stability for more than six treatment cycles in seven others. This suggests it might help control tumor growth and extend the time the disease remains under control. Cabozantinib blocks certain proteins that aid tumor growth and spread, making it a promising option for hard-to-treat cancers like neuroblastomas. Based on past results, cabozantinib could be a potential treatment for high-risk pediatric cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Nilay Shah

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults (18 months to under 40 years) with high-risk pediatric solid tumors like sarcoma or neuroblastoma, especially if they're at risk of recurrence. Participants need good organ function, no recent surgeries or biopsies, and must be able to swallow tablets. They should not be pregnant and must use contraception.

Inclusion Criteria

I haven't had any major surgeries in the last 4 weeks.

Patient must be able to start study treatment within specified timeframes

I have seizures but am on a stable medication regimen for them.

Exclusion Criteria

See protocol for additional exclusion criteria

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib for up to 12 months in 28-day cycles

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

5-8 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib

Trial Overview The study tests Cabozantinib as a maintenance therapy in patients with minimal disease burden from specific pediatric cancers. It aims to prevent or delay tumor regrowth after initial treatment success, potentially extending disease control or achieving long-term cure.

How Is the Trial Designed?

Group I: Cabozantinib Experimental Treatment 1 Intervention

Enrolled patients will be treated with cabozantinib maleate, tablet formulation, using the recommended Phase 2 dose of 40 mg/m2/day, to a maximum of 420 mg/week. Treatment will be administered in 28- day cycles.

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?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

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, an inhibitor of multiple receptor tyrosine kinases, has been shown to significantly prolong overall survival and progression-free survival in patients with advanced hepatocellular carcinoma (HCC) who have previously been treated with sorafenib, based on the CELESTIAL phase 3 trial.

The tolerability profile of cabozantinib is acceptable, with manageable adverse events that can be addressed through dose modifications and supportive care, making it a viable treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Review in Advanced Hepatocellular Carcinoma. Deeks, ED.[2020]

Cabozantinib, a tyrosine kinase inhibitor targeting the MET oncoprotein, showed significant disease regression and symptom improvement in two pediatric patients with advanced-stage renal cell carcinoma (RCC) over a period of more than 15 months.

This case report suggests that cabozantinib may provide prolonged disease control in children with RCC, indicating a need for further research into its efficacy and safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal cell carcinoma. Wedekind, MF., Ranalli, M., Shah, N.[2017]

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 (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]

The landscape of pediatric oncology drug development is evolving with new treatment therapies and innovative clinical trial designs, such as the iMATRIX platform, which allows for concurrent study of multiple drugs across various pediatric tumors.

Despite these advancements, the approval process for new pediatric cancer drugs remains slow, highlighting the need for faster regulatory pathways to ensure timely access to effective treatments for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing drug development in pediatric oncology, a focus on cancer biology and targeted therapies: iMATRIX platform. Uguen, M., Hilton, M., Farid-Kapadia, M., et al.[2023]

Antiangiogenic agents, which target blood vessel growth, are being explored for treating childhood cancers, but their development is complicated by concerns about potential toxicities in growing children.

The safety and efficacy of these agents, particularly VEGF inhibitors, may differ between adults and children, necessitating careful evaluation of their long-term effects on cardiovascular, endocrine, and bone health before use in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of VEGF signaling pathway inhibitors in childhood solid tumors. Glade Bender, J., Yamashiro, DJ., Fox, E.[2023]

Cabozantinib (Cabometyx) has received approval for the treatment of locally advanced or metastatic differentiated thyroid cancer that has not responded to previous therapies targeting vascular endothelial growth factor receptors.

This approval highlights Cabozantinib's efficacy in addressing a specific type of thyroid cancer that has progressed after other treatments, providing a new option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Cabozantinib. Aschenbrenner, DS.[2023]

In a phase 1 trial involving 41 children with refractory solid tumors, the maximum tolerated dose (MTD) of cabozantinib was determined to be 40 mg/m2/day, with dose-limiting toxicities including palmar-plantar erythrodysesthesia syndrome and elevated liver enzymes.

The trial showed preliminary efficacy, with four patients achieving a confirmed partial response and seven maintaining stable disease for over six cycles, indicating potential therapeutic activity of cabozantinib in this pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of cabozantinib in children and adolescents with recurrent or refractory solid tumors, including CNS tumors: Trial ADVL1211, a report from the Children's Oncology Group. Chuk, MK., Widemann, BC., Minard, CG., et al.[2020]

Over 80% of children with cancer now survive for at least 5 years, but cancer remains the leading cause of disease-related death in children, highlighting the need for continued advancements in treatment.

The introduction of targeted therapies, like imatinib mesylate for specific types of leukemia, has improved outcomes, but challenges remain in understanding drug toxicity in children and developing pediatric-specific formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the outcome for children with cancer: Development of targeted new agents. Adamson, PC.[2022]

In a real-world study of 206 lung cancer patients, 18% experienced cardiotoxicity, with QTc prolongation being the most common type, highlighting a significant risk associated with tyrosine-kinase inhibitors like osimertinib and crizotinib.

The study found that none of the patients who developed cardiotoxicity would have qualified for certain phase 3 clinical trials, suggesting that these trials may underestimate the true risk of cardiotoxicity in broader patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the efficacy of osimertinib and crizotinib in phase 3 clinical trials on anti-cancer treatment-induced cardiotoxicity: are real-world studies the way forward? Kobat, H., Elkonaissi, I., Foreman, E., et al.[2023]

In a retrospective analysis of 16 adult patients with advanced osteosarcoma and Ewing sarcoma, cabozantinib showed antitumor activity, with 9 out of 16 patients achieving stable disease and a median progression-free survival of 5 months.

While cabozantinib was associated with common side effects like fatigue and weight loss, it also resulted in one serious adverse event (cerebral hemorrhage), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data on Cabozantinib in Advanced Osteosarcoma and Ewing Sarcoma Patients: A Study from the Hellenic Group of Sarcoma and Rare Cancers. Kokkali, S., Kyriazoglou, A., Mangou, E., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6082380/

A Phase 1 Study of Cabozantinib in Children and Adolescents ... The recommended dose of cabozantinib in pediatric patients with refractory solid tumors is 40 mg/m 2 /day. A phase 2 study of cabozantinib is being conducted.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05135975

NCT05135975 | A Study of Cabozantinib as a Maintenance ... The study proposes to evaluate the efficacy of up to one year of treatment with cabozantinib in pediatric solid tumors after completion of last therapy with a ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.10010

Phase 2 trial of cabozantinib in children and young adults ... We conducted a multi-center open label phase 2 trial to determine the activity of cabozantinib in select pediatric solid tumors.

4. withpower.com withpower.com/trial/phase-3-sarcoma-9-2021-83196

Cabozantinib for Childhood Cancer The trial showed preliminary efficacy, with four patients achieving a confirmed partial response and seven maintaining stable disease for over six cycles, ...

5. 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 and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established. Please see accompanying ...

6. cabometyxhcp.com cabometyxhcp.com/rcc-treatment/monotherapy/safety

CABOSUN & METEOR show similar safety results for ... No new safety signals observed between METEOR and CABOSUN trials · Laboratory abnormalities occurring in ≥25% of patients in the CABOMETYX arm of the METEOR ...

7. ema.europa.eu ema.europa.eu/en/documents/product-information/cabometyx-epar-product-information_en.pdf

Cabometyx, INN-Cabozantinib - European Medicines Agency Paediatric population. The safety and efficacy of cabozantinib in children and adolescents aged <18 years have not yet been established. Currently available ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/208692s012lbl.pdf

cabometyx - accessdata.fda.gov The safety and effectiveness of CABOMETYX for the treatment of differentiated thyroid cancer. (DTC) have been established in pediatric patients aged 12 years ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5905684/

Management of Adverse Events Associated with ... This review reports on the safety profile of cabozantinib in patients with advanced renal cell carcinoma and offers guidance on the management of adverse ...

10. cabometyx.com cabometyx.com/

CABOMETYX® (cabozantinib) Patient Website ... CABOMETYX is safe and effective in children younger than 12 years of age. Indications. People with kidney cancer (renal cell carcinoma). CABOMETYX may be used:.