Cabozantinib + Supportive Care for Bone Cancer

(CabOSTar Trial)

Recruiting at 72 trial locations

Overseen By Ipsen Clinical Study Enquiries

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Ipsen

Must not be taking: Kinase inhibitors

Disqualifiers: Low grade osteosarcoma, Brain metastases, 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: 24 months

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The participants of this study will be children, adolescents, and young adults with residual osteosarcoma, which cannot be removed completely through surgery. Participants will have achieved a partial response or stable disease at the end of conventional chemotherapy. Osteosarcoma is cancer of the bone. The cancer cells make immature bone cells, known as osteoid. Osteosarcoma is very rare, but it is the most common type of bone cancer in children and teens. It is most common in teens and young adults. In this study, participants will receive either cabozantinib and best supportive care or the best supportive care alone. Best supportive care will be provided at the investigator's discretion and according to institutional guidelines. It includes antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including radiotherapy), etc. but does not include tumor specific therapy. Cabozantinib will be taken by mouth (orally), as a tablet, once a day. Cabozantinib will be provided to participants who tolerate it for as long as their disease does not progress. Participants in the study receiving best supportive care alone may switch to treatment with cabozantinib and best supportive care if their disease progresses and if other eligibility criteria are met. Participants may withdraw consent to participate at any time. The estimated duration of the study for participants is 24 months, however a participant could remain in the study longer if demonstrating treatment benefit.

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 have taken certain cancer treatments or small molecule kinase inhibitors recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug cabozantinib for bone cancer?

Research shows that cabozantinib can improve overall survival in patients with bone metastases, reducing the risk of death by 53% compared to standard care. Additionally, in a study of patients with advanced osteosarcoma and Ewing sarcoma, cabozantinib showed antitumor activity, with some patients experiencing stable disease outcomes. ^{1 2 3 4 5}

Is Cabozantinib safe for humans?

Cabozantinib has been tested in various cancers, and common side effects include fatigue, diarrhea, high blood pressure, and skin reactions on the hands and feet. In some cases, serious side effects like cerebral hemorrhage (bleeding in the brain) have occurred, requiring dose adjustments. ^{2 4 5 6 7}

What makes the drug Cabozantinib unique for treating bone cancer?

Cabozantinib is unique because it targets multiple pathways involved in cancer growth, including those related to blood vessel formation and cell signaling, which may help in managing bone cancer. It has shown potential benefits in patients with advanced bone sarcomas, offering a new option where limited treatments exist. ^{1 2 6 8 9}

Research Team

Ipsen Medical Director

Principal Investigator

Ipsen

Eligibility Criteria

This trial is for children and young adults aged 5 to 30 with high-grade osteosarcoma that's not fully removable by surgery. They should have stable disease after chemotherapy, a life expectancy over 6 months, good performance status, and proper organ/marrow function. Those with progressive disease or severe side effects from previous treatments are excluded.

Inclusion Criteria

My cancer can be measured or evaluated using specific criteria.

I finished my last chemotherapy between 4 weeks and 2 months ago.

Life expectancy >6 months

Exclusion Criteria

I do not have any severe, uncontrolled illnesses.

Pregnancy or breast-feeding

Participants who in the opinion of the investigator may not be able to comply with the requirements of the study are not eligible

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib and best supportive care or best supportive care alone. Cabozantinib is taken orally once a day.

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue treatment with cabozantinib and best supportive care if demonstrating treatment benefit

Long-term

Treatment Details

Interventions

• Best Supportive Care (BSC)
• Cabozantinib

Trial Overview The study compares the effectiveness of Cabozantinib taken orally plus Best Supportive Care (BSC) versus BSC alone in managing osteosarcoma. BSC includes symptom control and pain management but no tumor-specific therapy. Participants can switch to Cabozantinib if their condition worsens.

Participant Groups

Group I: Arm B: Best supportive care (BSC) Experimental Treatment 1 Intervention

Participants will receive BSC alone administered per investigator's discretion and institutional guidelines.

Group II: Arm A: Cabozantinib+ Best supportive care (BSC) Experimental Treatment 2 Interventions

Participants will receive cabozantinib and BSC.

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?

Ipsen

Lead Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Findings from Research

Cabozantinib significantly improves overall survival in cancer patients, reducing the risk of death by 53% for those with bone metastases and by 44% for those without, based on a systematic review of randomized trials.

While cabozantinib is an effective treatment option for patients with bone metastases, its benefits do not differ significantly from those seen in patients without bone metastases, suggesting that the presence of bone metastases should not be the primary factor in choosing this drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A metanalysis on cabozantinib and bone metastases: true story or commercial gimmick? Bersanelli, M., Buti, S., Ghidini, A., et al.[2021]

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]

A patient with metastatic mesenchymal chondrosarcoma showed significant clinical improvement and a good partial response to treatment with cabozantinib over one year, suggesting potential efficacy of this multi-tyrosine kinase inhibitor for this aggressive cancer.

Current standard treatments for mesenchymal chondrosarcoma, based on Ewing sarcoma protocols, have low survival rates, highlighting the need for alternative therapies like cabozantinib, especially for tumors with similar genetic characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic mesenchymal chondrosarcoma showing a sustained response to cabozantinib: A case report. Blum, V., Andrei, V., Ameline, B., et al.[2023]

In a Phase 1 study involving 12 patients with relapsed osteosarcoma and Ewing sarcoma, the combination of cabozantinib, topotecan, and cyclophosphamide showed acceptable toxicity levels, with manageable dose-limiting toxicities observed.

The treatment resulted in one partial response and stable disease in seven patients, suggesting that this combination therapy may provide potential disease control in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. Campbell, K., Posner, A., Chen, N., et al.[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]

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 is an oral multitargeted tyrosine kinase inhibitor approved for advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, showing potential advantages over single-receptor TKIs.

The article reviews clinical trial data and management strategies for common adverse events associated with cabozantinib, highlighting its expanding use in treating various cancers such as prostate, hepatocellular, and lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. Markowitz, JN., Fancher, KM.[2019]

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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

A metanalysis on cabozantinib and bone metastases: true story or commercial gimmick? [2021]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Metastatic mesenchymal chondrosarcoma showing a sustained response to cabozantinib: A case report. [2023]

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

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. [2023]

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

New Indication for Cabozantinib. [2023]

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

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

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

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. [2019]

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

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

9. France pubmed.ncbi.nlm.nih.gov

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