Metastatic Ewing's Trial Testing Schedule Enhancement to Improve Outcomes

Inclusion Criteria: * Patients must be \>1 year of age. There is no upper age limit. * Patients, in the opinion of the enrolling investigator, must be healthy enough to tolerate protocol therapy. * Patients must have a new histologic diagnosis of either: widely metastatic Ewing sarcoma or metastatic CIC-rearranged sarcoma. * Patients must have sufficient tissue submitted (flash frozen tissue, FFPE block, or up to 10 unstained FFPE slides) for correlative testing. This may be from a primary or metastatic site. * Patients must not have received any prior systemic therapy with the exception that they may have started an initial cycle of vincristine/doxorubicin/cyclophosphamide (VDC) prior to enrollment, i.e. VDC may have been given, but not ifosfamide/etoposide (IE). * Adequate organ function. * Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment or abstinence. * All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document. Exclusion Criteria: * Patients with localized disease or lung only metastases for Ewing sarcoma or localized disease for CIC-rearranged sarcomas. * Patients with central nervous system (CNS) tumors (primary or metastatic) are not eligible. * Patients who are receiving any other investigational agents for their cancer. * Patients with a his…