A Feasibility and Randomized Phase 2/3 Study of the VEGFR2/MET Inhibitor Cabozantinib in Combination With Cytotoxic Chemotherapy for Newly Diagnosed Osteosarcoma
National Cancer Institute (NCI)
Summary
This phase II/III trial tests the safety, side effects, and best dose of the drug cabozantinib in combination with standard chemotherapy, and to compare the effect of adding cabozantinib to standard chemotherapy alone in treating patients with newly diagnosed osteosarcoma. Cabozantinib is in a class of medications called kinase inhibitors which block protein signals affecting new blood vessel formation and the ability to activate growth signaling pathways. This may help slow the growth of tumor cells. The drugs used in standard chemotherapy for this trial are methotrexate, doxorubicin, and cisplatin (MAP). Methotrexate stops cells from making DNA and may kill tumor cells. It is a type of antimetabolite. Doxorubicin is in a class of medications called anthracyclines. It works by slowing or stopping the growth of tumor cells in the body. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Adding cabozantinib to standard chemotherapy may work better in treating newly diagnosed osteosarcoma.
Description
PRIMARY OBJECTIVES: I. To determine the feasibility of adding cabozantinib S-malate (cabozantinib) to standard MAP (high dose methotrexate, doxorubicin hydrochloride \[doxorubicin\], and cisplatin) chemotherapy in patients with newly diagnosed metastatic osteosarcoma with a resectable primary tumor. II. To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survival (EFS) than MAP chemotherapy alone in patients with localized, resectable osteosarcoma. III. To determine whether MAP chemotherapy plus cabozantinib results in more favorable event-free survi…
Eligibility
- Age range
- Up to 40 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must be \< 40 years of age at the time of enrollment. * Patients must have a body surface area of \>= 0.8 m\^2 at the time of enrollment. * Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies. * Feasibility Phase (NOTE: as of Amendment #2B, the feasibility phase has been completed) P…
Interventions
- ProcedureBone Scan
Undergo bone scintography
- DrugCabozantinib S-malate
Given PO
- DrugCisplatin
Given IV
- ProcedureComputed Tomography
Undergo CT
- DrugDoxorubicin Hydrochloride
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugMethotrexate
Given IV
Locations (194)
- Children's Hospital of AlabamaBirmingham, Alabama
- Banner Children's at DesertMesa, Arizona
- Phoenix Childrens HospitalPhoenix, Arizona
- Mayo Clinic Hospital in ArizonaPhoenix, Arizona
- Banner University Medical Center - TucsonTucson, Arizona
- Arkansas Children's HospitalLittle Rock, Arkansas