The researchers are doing this study to find out whether adding gefitinib, trametinib, disulfiram, and sunitinib to standard chemotherapy is a more effective treatment approach for people with osteosarcoma than standard chemotherapy on its own. The researchers will also look at the safety of adding these drugs to standard chemotherapy. The researchers will also use the additional research biopsies from Cohort 1 participants to learn more about how osteosarcoma survives during chemotherapy.
Having at least 1 extrapulmonary metastasis, radiographic confirmation of metastasis is adequate, and/or
Unresectable metastases at diagnosis as determined by the investigator
Patients may have started systemic conventional chemotherapy but must enroll on this study prior to day 29 of chemotherapy initiation. Having received a single standard MAP cycle (AP x 1 and HDMTX up to 2 times) of chemotherapy prior to enrollment is acceptable
Patients with newly diagnosed osteosarcoma who are not eligible for Cohorts 1 or 2.
Patients who are receiving any other investigational agents for osteosarcoma therapy are ineligible.
Patient with an uncontrolled chronic or active infection or another condition where any component of OstEvo therapy would be contraindicated.
Patients with a history of heart disease including, but not limited to: uncontrolled hypertension within 12 months prior to enrollment; ongoing cardiac dysrhythmias ≥ grade 2 or atrial fibrillation of any grade; unstable angina, symptomatic congestive heart failure, or prior myocardial infarction.
Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis-based products would not be a reason for exclusion.
Parallel
Methotrexate
DrugMethotrexate 12 g/m\^2 (max dose 20 grams) intravenously over 4 hours or as per institutional standard.
Doxorubicin
DrugDoxorubicin 37.5 mg/m\^2 intravenously over 15 to 30 minutes or as per institutional standard.
Cisplatin
DrugCisplatin 60 mg/m\^2 intravenously over 4 hours or as per institutional standard.
Gefitinib
DrugGefitinib 400 mg/m\^2/dose (maximum dose 250 mg) orally daily for 14 days (14 doses)
Trametinib
DrugTrametinib will be dispensed as per institutional standard.
Disulfiram
DrugDisulfiram 250 to 500 mg orally once daily for 14 days
Sunitinib
DrugSunitinib capsules for under 18 years of age: 15 mg/m\^2/dose (maximum 50 mg) orally once daily x 14 days
Ifosfamide
DrugIfosfamide 2,800 mg/m\^2 intravenously as per institutional standard.
Biopsy
Procedure/SurgeryResearch biopsy prior to therapy
12-month progression free survival (PFS) (cohort 1)
Response will be determined by the investigator and progression will be guided by RECIST 1.1 criteria
24-month overall survival (OS) (cohort 2)
Response will be determined by the investigator and progression will be guided by RECIST 1.1 criteria
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