Cabozantinib + Ifosfamide for Bone Cancer
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Children's Hospital of Philadelphia
Must not be taking: CYP3A4 drugs, QTc drugs
Disqualifiers: Brain metastases, Cardiovascular disease, others
No Placebo Group
Breakthrough Therapy
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
The purpose of this study is to better understand how safe and effective the drug cabozantinib in combination with high-dose ifosfamide is in the treatment of children and adults with relapsed/refractory Ewing sarcoma and osteosarcoma.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but it does exclude certain medications like strong CYP3A4 inducers or inhibitors, and some anticoagulants. It's best to discuss your current medications with the study team to see if they are allowed.
What data supports the effectiveness of the drug Cabozantinib for bone cancer?
Research shows that Cabozantinib has been effective in reducing tumor size in patients with bone metastases from various cancers, including sarcoma, and has improved overall survival rates. In a study, it decreased the risk of death by 53% in patients with bone metastases compared to standard treatments.12345
Is the combination of Cabozantinib and Ifosfamide safe for treating bone cancer?
Cabozantinib has been studied for safety in various cancers, including bone cancers like osteosarcoma and Ewing sarcoma. Common side effects include fatigue, diarrhea, and high blood pressure, with some serious risks like cerebral hemorrhage. Dose adjustments are often needed to manage these side effects.12678
How is the drug Cabozantinib + Ifosfamide unique for treating bone cancer?
Cabozantinib, when combined with Ifosfamide, offers a novel approach for bone cancer by potentially targeting cancer growth through different mechanisms, as Cabozantinib is known to inhibit certain pathways involved in tumor growth and blood vessel formation, which is different from traditional chemotherapy regimens that primarily focus on killing rapidly dividing cells.910111213
Research Team
Theodore W. Laetsch
Principal Investigator
Children's Hospital of Philadelphia
Eligibility Criteria
This trial is for children and adults with relapsed/refractory Ewing sarcoma or osteosarcoma who have had prior chemotherapy. Participants must be able to swallow tablets, not pregnant, use contraception, and have a certain body surface area. They should have measurable disease progression but limited previous treatments and good organ function.Inclusion Criteria
My cancer can be measured by scans according to specific criteria.
Hematopoietic function: Absolute neutrophil count > 1,000/uL (without hematopoietic growth factor within the time frame noted below). Hemoglobin > 8 g/dL (without transfusion in the last 7 days). Platelets > 100,000/uL (without transfusion in the last 7 days).
My kidney function is normal based on tests.
See 10 more
Exclusion Criteria
Other clinically significant disorders that would preclude safe study participation, including: Cavitating pulmonary lesion. Serious non-healing wound/ulcer/bone fracture. Uncompensated/symptomatic hypothyroidism. Moderate to severe hepatic impairment (Child-Pugh B or C). Recipient of solid organ transplant, known human immunodeficiency virus (HIV) seropositivity, and other non-treatment related immunodeficiencies. Severe or uncontrolled infection or systemic disease. Inadequate electrolyte balance, defined as abnormal levels of serum potassium, calcium, magnesium, and phosphorous and causing clinically significant symptoms, acid-base disturbances, or changes in ECG. Women who are currently pregnant or breastfeeding.
I have had severe bladder inflammation from cancer treatment.
I am not taking any strong medication that affects liver enzymes or prolongs the QT interval.
See 17 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive cabozantinib in combination with high-dose ifosfamide to evaluate safety and antitumor activity
6 months
Periodic visits for disease progression assessment
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Extension
Participants may continue treatment to further evaluate long-term safety and efficacy
Long-term
Treatment Details
Interventions
- Cabozantinib (Tyrosine Kinase Inhibitor)
Trial OverviewThe study tests the safety and effectiveness of cabozantinib combined with high-dose ifosfamide in treating specific sarcomas. It aims to understand how well this drug combination works when other treatments haven't been successful.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment1 Intervention
Cabozantinib
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 NearbySelect from list below to view details:
Children's Hospital ColoradoAurora, CO
University of ColoradoAurora, CO
University of PennsylvaniaPhiladelphia, PA
Children's Hospital of PhiladelphiaPhiladelphia, PA
More Trial Locations
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Who Is Running the Clinical Trial?
Children's Hospital of Philadelphia
Lead Sponsor
Trials
749
Patients Recruited
11,400,000+
Children's Hospital Colorado
Collaborator
Trials
121
Patients Recruited
5,135,000+
Alex's Lemonade Stand Foundation
Industry Sponsor
Trials
9
Patients Recruited
1,500+
Exelixis
Industry Sponsor
Trials
126
Patients Recruited
20,500+
Findings from Research
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]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma.Noh, JJ., Cho, YJ., Ryu, JY., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase II Study of Cabozantinib in Patients With Bone Metastasis.Choy, E., Cote, GM., Michaelson, MD., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases.Xu, J., Higgins, MJ., Tolaney, SM., et al.[2021]
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 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]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives.Trojan, J.[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]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.Harris, MB., Gieser, P., Goorin, AM., et al.[2017]
A combination chemotherapy regimen of ifosfamide, doxorubicin, and cisplatin was assessed in 103 patients with primary osteosarcoma, showing a clinical response in 36% of primary tumors and 33% of pulmonary metastases.
Despite the regimen's activity, it did not demonstrate superior efficacy compared to the existing two-drug cisplatin-doxorubicin treatment, with five-year survival rates of 62% for non-metastatic limb tumors, 41% for axial skeletal tumors, and only 16% for limb metastatic cases.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma. European Osteosarcoma Intergroup (EOI).Voûte, PA., Souhami, RL., Nooij, M., et al.[2020]
In a study of 69 patients with untreated osteosarcoma, the combination of carboplatin and ifosfamide showed a 67.7% clinical and radiographic response rate, significantly reducing the rate of disease progression compared to historical data using only ifosfamide.
Patients receiving carboplatin/ifosfamide experienced comparable survival rates to those treated with cisplatin-based therapies, but with reduced long-term renal toxicity and ototoxicity, indicating a safer treatment option.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.Meyer, WH., Pratt, CB., Poquette, CA., et al.[2017]
The combination of etoposide and high-dose ifosfamide resulted in a 59% overall response rate in patients with newly diagnosed metastatic osteosarcoma, indicating its effectiveness as an induction chemotherapy.
Despite its efficacy, the treatment was associated with significant toxicity, including severe myelosuppression (83% of patients experienced grade 4 neutropenia) and complications such as sepsis and renal toxicity, highlighting the need for careful monitoring during therapy.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial.Goorin, AM., Harris, MB., Bernstein, M., et al.[2017]
In a study of 86 osteosarcoma patients, the combination of liposome doxorubicin and ifosfamide resulted in a higher total effective rate and 2-year survival rate compared to conventional doxorubicin and ifosfamide, indicating improved efficacy.
Patients receiving liposome doxorubicin experienced fewer adverse effects, such as liver and kidney function injuries and cardiotoxicity, while also showing better quality of life scores, suggesting a safer treatment option.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Efficacy of ifosfamide combined with liposome doxorubicin on osteosarcoma and its effects on serum IL-10, TNF-α, and IFN-γ in patients with osteosarcoma.Huang, G., Hua, S., Liu, H., et al.[2022]
References
Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. [2023]
Anticancer Activity of the Combination of Cabozantinib and Temozolomide in Uterine Sarcoma. [2022]
Phase II Study of Cabozantinib in Patients With Bone Metastasis. [2022]
A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases. [2021]
A metanalysis on cabozantinib and bone metastases: true story or commercial gimmick? [2021]
Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. [2019]
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. [2021]
Real-World Data on Cabozantinib in Advanced Osteosarcoma and Ewing Sarcoma Patients: A Study from the Hellenic Group of Sarcoma and Rare Cancers. [2023]
Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. [2017]
A phase II study of cisplatin, ifosfamide and doxorubicin in operable primary, axial skeletal and metastatic osteosarcoma. European Osteosarcoma Intergroup (EOI). [2020]
Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial. [2017]
Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial. [2017]
Efficacy of ifosfamide combined with liposome doxorubicin on osteosarcoma and its effects on serum IL-10, TNF-α, and IFN-γ in patients with osteosarcoma. [2022]