Cabozantinib for Childhood Cancer

Recruiting in Palo Alto (17 mi)

+5 other locations

Overseen by Nilay Shah

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Nationwide Children's Hospital

Must not be taking: Anticancer agents, Anticonvulsants

Disqualifiers: Major surgery, Myocardial infarction, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study will expand the types of pediatric cancers being evaluated for response to cabozantinib. The current COG study is restricted to Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, Wilms tumor, and a handful of uncommon tumors. The proposed study will extend this evaluation to tumors that have been shown to either express known targets of cabozantinib or with preclinical evidence of efficacy, including specifically neuroblastomas. These tumors have high morbidity and mortality, particularly in the relapse setting, and few or no proven therapeutic options. As such, evaluation of cabozantinib in these studies is warranted. The study hypothesizes that use of cabozantinib in patients with ultra-high-risk pediatric solid tumors with minimal disease burden, as defined in the inclusion criteria below, can prevent and/or slow recurrent tumor formation in pediatric solid tumors and thereby significantly extend the period of disease control and/or induce a durable cure.

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.

What data supports the effectiveness of the drug Cabozantinib for childhood cancer?

Cabozantinib has shown effectiveness in treating advanced renal cell carcinoma in adults and has been associated with disease control in pediatric patients with recurrent renal cell carcinoma. Additionally, it has demonstrated antitumor activity in advanced osteosarcoma and Ewing sarcoma, suggesting potential benefits for childhood cancers. ^{1 2 3 4 5}

Is cabozantinib safe for children with cancer?

A phase 1 study found that cabozantinib was tested in children with solid tumors to determine the maximum tolerated dose and its safety profile. The study looked at side effects and how the drug behaves in the body, which helps understand its safety in children. ^{3 6 7 8 9}

How is the drug Cabozantinib unique for treating childhood cancer?

Cabozantinib is unique because it targets multiple pathways involved in cancer growth, specifically inhibiting proteins like MET, VEGF, and AXL, which are not commonly targeted together in other treatments. This makes it a novel option for childhood cancers, especially when standard treatments are limited or ineffective. ^{1 4 5 10 11}

Research Team

Nilay Shah

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Cabozantinib (Tyrosine Kinase Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Children's Hospital of Alabama/UAB Birmingham, AL

Children's Hospital of Colorado Aurora, CO

Primary Children's Hospital Salt Lake City, UT

Children's National Medical Center Washington, United States

More Trial Locations

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Timothy C. Robinson

Nationwide Children's Hospital

Chief Executive Officer since 2019

BSc in Psychology and Business Administration from Indiana University

Catherine Krawczeski

Nationwide Children's Hospital

Chief Medical Officer

MD

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 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]

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]

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]

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]

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]

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]

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]

References

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

New Indication for Cabozantinib. [2023]

2. Switzerland 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. [2023]

3. United States 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. [2020]

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

Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal cell carcinoma. [2017]

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Clinical development of VEGF signaling pathway inhibitors in childhood solid tumors. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Advancing drug development in pediatric oncology, a focus on cancer biology and targeted therapies: iMATRIX platform. [2023]

9. England 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? [2023]

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

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

11. France pubmed.ncbi.nlm.nih.gov

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