Cabozantinib + Supportive Care for Bone Cancer

(CabOSTar Trial)

Recruiting at 82 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called cabozantinib (also known as Cabometyx) for children, teens, and young adults with osteosarcoma that cannot be fully removed by surgery. The study aims to determine if cabozantinib, combined with supportive care (such as pain management and nutritional support), is more effective than supportive care alone. Participants should have already undergone chemotherapy and have stable disease or a partial response, meaning the cancer has not progressed since their last treatment. This trial may suit those with osteosarcoma seeking new treatment options after chemotherapy. Participants can choose to leave the study at any time. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to explore new treatment possibilities.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cabozantinib is safe for patients with bone cancer. In earlier studies, cabozantinib slowed the disease or reduced the risk of death by 40%. It also caused tumors to shrink or stop growing in 23% of cases.

Cabozantinib has been tested in various situations, including when cancer has spread to the bones. While it shows promise, some patients experienced side effects from the treatment. These side effects can include fatigue, diarrhea, and loss of appetite. Participants should discuss with their doctors how to manage these possible side effects.

Overall, cabozantinib has undergone extensive study and continues to be researched to ensure its efficacy and safety, especially for patients with challenging conditions like osteosarcoma. ^{1 2 3 4 5}

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

Unlike the standard treatments for bone cancer, which often involve chemotherapy, radiation, and surgery, cabozantinib offers a novel approach by interfering with multiple pathways that tumors use to grow and spread. This drug specifically targets and inhibits the activity of proteins like MET and VEGFR2, which are involved in tumor growth and blood vessel formation. Researchers are excited because cabozantinib has shown promise in reducing tumor size and slowing disease progression, potentially offering a more targeted and effective treatment option for patients with bone cancer.

What evidence suggests that this trial's treatments could be effective for osteosarcoma?

Research has shown that cabozantinib may help treat cancers affecting the bones. Studies found that cabozantinib shrank tumors that had spread to the bones. In patients with advanced prostate cancer, it improved bone scans and slowed disease progression. Another study found that cabozantinib, when combined with other treatments, extended the time patients lived without their cancer worsening. In this trial, one group will receive cabozantinib with best supportive care (BSC), while another group will receive BSC alone. These findings suggest that cabozantinib could manage osteosarcoma by targeting cancer cells in the bone. ^{1 3 4 5 6}

Who Is on the Research Team?

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

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

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

I do not have any severe, uncontrolled illnesses.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9256024/

Phase II Study of Cabozantinib in Patients With Bone Metastasis Surprisingly, we also observed that cabozantinib had anti-tumor activity as determined by frequent and significant reductions in measurements of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8802308/

Efficacy and Effect of Cabozantinib on Bone Metastases in ... Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes ...

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-final-five-year-follow-results-checkmate-9er

9ER Trial Evaluating CABOMETYX® (cabozantinib ... - Exelixis At a median follow-up of 67.6 months, CABOMETYX in combination with Opdivo improved progression-free survival (PFS; hazard ratio [HR]: 0.58; 95% ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.535

Evaluating the efficacy of cabozantinib in patients with ... Conclusions: Cabozantinib demonstrated favorable clinical effects on bone metastasis in patients with aRCC, as suggested by a high DCR. Our ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1558767323002173

Real-World Results of Cabozantinib Given as Alternative ... The aim of this retrospective study was to analyze the pattern of cabozantinib treatment and its efficacy in a real-world cohort of patients with mRCC. More ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11332639/

The efficacy and safety of cabozantinib in patients ... Positive results were observed for cabozantinib, with a 40% reduction in disease progression or death and a 23% tumor response rate compared to ...