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 history of cancer that was treated with myelosuppressive chemotherapy or radiation therapy.
* Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer.
* Patients are ineligible if they have uncontrolled intercurrent illness.
* Pregnancy or Breast Feeding: Pregnant or breast-feeding women will not be entered on this study, because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to starting protocol therapy.
* Patients who are considered unable to comply with the safety monitoring requirements of the study are not eligible.