Cabozantinib + Supportive Care for Bone Cancer
(CabOSTar Trial)
Recruiting in Palo Alto (17 mi)
+69 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ipsen
Must not be taking: Kinase inhibitors
Disqualifiers: Low grade osteosarcoma, Brain metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 Jurisdictions
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.
12345Is 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.
24567What 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.
12689Eligibility 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
+11 more
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
+10 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Arm B: Best supportive care (BSC)Experimental Treatment1 Intervention
Participants will receive BSC alone administered per investigator's discretion and institutional guidelines.
Group II: Arm A: Cabozantinib+ Best supportive care (BSC)Experimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Southern California (USC) - Norris Cancer HospitalLos Angeles, CA
Anderson Children's HospitalHouston, TX
Cincinnati Children's Hospital Medical Center - Cancer and Blood Diseases Institute (CBDI)Cincinnati, OH
Princess Margaret cancer centerToronto, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
IpsenLead Sponsor
References
A metanalysis on cabozantinib and bone metastases: true story or commercial gimmick? [2021]Is it true that cabozantinib should be the preferred option treating patients with bone metastases? Are there any reliable comparisons between this drug and other standard options in this subgroup? To address the issue, we performed a systematic review and metanalysis of randomized trials with cabozantinib, to assess its effectiveness, in terms of overall survival, according to the presence of bone metastases. We included (a) randomized controlled trials; (b) any solid tumors and therapeutic line; and (c) overall survival data available according to the site of disease. Cabozantinib improved overall survival both for the group with bone metastases, with risk of death decreased by 53% (hazard ratio, 0.47; 95% confidence interval, 0.26-0.87; P=0.02) and for the group without bone metastases, decreasing the risk of death by 44% (hazard ratio, 0.56; 95% confidence interval, 0.40-0.79; P=0.001) over the standard of care. The difference was not significantly different between the two groups. Despite cabozantinib can be undoubtedly listed as a good therapeutic option for cancer patients with bone metastases, it seems that its preclinical profile against bone remodeling does not translate into an actual clinical relevance, preventing from considering the presence of bone metastases as principal criterion for the choice of this drug.
Real-World Data on Cabozantinib in Advanced Osteosarcoma and Ewing Sarcoma Patients: A Study from the Hellenic Group of Sarcoma and Rare Cancers. [2023]Advanced osteosarcomas (OSs) and Ewing sarcomas (ESs) tend to have poor prognosis with limited therapeutic options beyond first-line therapy. Aberrant angiogenesis and MET signaling play an important role in preclinical models. The anti-angiogenic drug cabozantinib was tested in a phase 2 trial of advanced OS and ES and was associated with clinical benefits. We retrospectively analyzed the off-label use of cabozantinib in adult patients with advanced OS and ES/primitive neuroectodermal tumors (PNETs) in three centers of the Hellenic Group of Sarcoma and Rare Cancers (HGSRC). Between April 2019 and January 2022, 16 patients started taking 60 mg of cabozantinib for advanced bone sarcoma or PNET. Median age at cabozantinib initiation was 31 years (17-83). All patients had received peri-operative chemotherapy for primary sarcoma and between 0 and 4 lines of treatment (median; 2.5) for advanced disease. The most common adverse effects included fatigue, anorexia, hypertransaminasemia, weight loss, and diarrhea. One toxic death was noted (cerebral hemorrhage). Dose reduction to 40 mg was required in 31.3% of the patients. No objective response was noted, and 9/16 patients exhibited stable disease outcomes. Progression-free survival varied from 1 to 8 (median; 5) months. Our study demonstrates that cabozantinib has antitumor activity in this population. In the real-life setting, we observed similar adverse events as in the CABONE study and in other neoplasms.
Metastatic mesenchymal chondrosarcoma showing a sustained response to cabozantinib: A case report. [2023]Mesenchymal chondrosarcoma is a rare and aggressive sarcoma subtype with high risk for distant metastases and poor prognosis. Currently NCCN- and ESMO-Guidelines recommend using Ewing sarcoma protocols as standard treatment. Nevertheless, in localized disease overall 5-year survival rates are below 50% whereas in metastatic spread median progression-free survival rates of only 5 months can be expected. Here we present a patient with metastatic osseous spread of mesenchymal chondrosarcoma that showed a sustained clinical improvement and a good partial response on imaging over a period of one year when treated with the multi-tyrosine kinase inhibitor cabozantinib. Although we cannot explain the exact mechanism underlying this treatment effect, tumors with similar genetic patterns might respond to the same therapy as well.
Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. [2023]Phase 1 study assessing the safety and toxicity of cabozantinib in combination with topotecan and cyclophosphamide for relapsed osteosarcoma and Ewing sarcoma.
New Indication for Cabozantinib. [2023]Cabozantinib (Cabometyx) is now approved to treat locally advanced or metastatic differentiated thyroid cancer that has progressed following prior vascular endothelial growth factor receptor-targeted therapy.
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. [2021]Cabozantinib (Cabometyx®) is a potent multikinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor 2, the mesenchymal-epithelial transition factor (MET) receptor, and the "anexelekto" (AXL) receptor tyrosine kinase. It is approved for the treatment of advanced hepatocellular carcinoma (HCC) after failure of sorafenib in Europe (since November 2018) and in the USA (since January 2019). The approval of cabozantinib was based on results of the randomized, placebo-controlled, phase 3 CELESTIAL trial in patients with unresectable HCC, who received one or two prior lines of treatment including sorafenib. At the second planned interim analysis, the trial was stopped, because the primary end point overall survival was clearly in favor for cabozantinib. Additionally, median progression-free survival was superior to placebo. The most common ≥ grade 3 relevant adverse events in patients with HCC treated with cabozantinib were palmar-plantar erythrodysesthesia, hypertension, fatigue, and diarrhea. In this review, current data on cabozantinib for the treatment of patients with advanced HCC, with a focus on the management of common adverse events and ongoing clinical trials, are discussed.
Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. [2019]Cabozantinib is an oral small-molecule multitargeted tyrosine kinase inhibitor (TKI) that may confer an advantage over other TKIs that target a single receptor. It was approved by the U.S. Food and Drug Administration for the treatment of both advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, and it is being investigated for a wide array of other malignancies. Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article. Common adverse events are reviewed, and management strategies for select adverse events are discussed. Implications for contemporary practitioners are also provided because use of this novel agent is likely to increase as more studies are completed.
Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use. [2020]Oral cabozantinib tablets (Cabometyx®) are an important option for the treatment of advanced renal cell carcinoma (RCC). Cabozantinib is an anti-angiogenic agent and potently inhibits multiple tyrosine kinases, including those implicated in the development of RCC. The previously approved indication of cabozantinib tablets (i.e. treatment of advanced RCC following prior VEGF-targeted therapy) has been extended to include the first-line treatment of advanced RCC in treatment-naïve adults with intermediate or poor risk (EU) and all patients with advanced RCC (USA). These label extensions are based on the results of a randomized, open-label phase 2 trial, in which adults with metastatic RCC of poor or intermediate risk received targeted first-line treatment with cabozantinib or standard-of-care sunitinib. Relative to sunitinib, cabozantinib significantly prolonged median progression-free survival (primary endpoint; investigator and independent assessments), and increased the objective response rate (investigator assessment). The tolerability profile of cabozantinib is comparable to those of other tyrosine kinase inhibitors, with adverse events being manageable with medical intervention, dosage reductions, treatment interruption and/or permanent discontinuation.
Cabozantinib: A Review in Advanced Hepatocellular Carcinoma. [2020]Cabozantinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) with roles in cancer pathogenesis. This review focuses on data relevant to the use of cabozantinib tablets (Cabometyx®) in the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with the multi-RTK inhibitor sorafenib, an indication for which cabozantinib tablets are approved in the EU and USA. Approval of cabozantinib in this setting was based largely on the findings of CELESTIAL, a phase 3 trial in adults with advanced HCC who had previously received sorafenib, had progressive disease after at least one systemic therapy and had received up to two systemic treatments for their advanced disease. Compared with placebo in this study, cabozantinib prolonged both overall survival and progression-free survival, with these findings largely unaffected by patient/disease characteristics. The tolerability profile of cabozantinib in CELESTIAL was acceptable and consistent with that of other multi-RTK inhibitors, with adverse events that were manageable with dose modification and supportive care. Thus, cabozantinib is a welcome additional treatment option for use in adults with HCC previously treated with sorafenib.