Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

Inclusion Criteria:

* Group A participants must be \<14 years of age at time of diagnosis of histologically proven non-pelvic localized Ewing sarcoma family of tumor (ESFT) involving the bone or soft tissue.
* Group B participants must have newly diagnosed of histologically proven ESFT involving the bone or soft tissue and at least one of the following: metastatic disease (must be biopsy proven), or pelvic primary, or ≥14 years of age at the time of diagnosis.
* OR Group B participants must be newly diagnosed with intra-abdominal, unresectable or metastatic desmoplastic small round cell tumor. Metastatic site must be biopsy proven.
* Age must be ≤25 years.
* Adequate bone marrow function defined as a peripheral absolute neutrophil count (ANC) ≥750/m\^3 and platelet count ≥75,000/m\^3 (no transfusion within 7 days of study enrollment). Patients with Ewing sarcoma metastatic to the bone marrow are not required to meet bone marrow criteria for study eligibility and are not evaluable for hematologic toxicity.
* Must have adequate renal function based on age.
* Must not have had prior chemotherapy or radiation therapy. Emergent radiotherapy to preserve vital organ function is permitted. Participants who receive emergent radiation will not be eligible for window therapy.
* Must have adequate hepatic function defined as total bilirubin ≤3.0 mg/dL.
* Must have adequate cardiac function defined as shortening fraction ≥28%.
* Females of childbearing potential and males able to father a child must be willing to practice acceptable methods of birth control to prevent pregnancy.
* Additional criteria for Group B participants who will receive upfront window therapy (does not apply to participants who opt out of window therapy):

  * Cytochrome P450 CYP3A4 active agents: Must not be taking any of the following potent CYP3A4 inducers or inhibitors within 1 week prior to study entry: azole antifungals (such as fluconazole, voriconazole, itraconazole, ketoconazole), rifampin, phenytoin, phenobarbitol, carbamazepine, grapefruit juice and St. John's wort.
  * Must have measurable disease.
  * Must not have received emergent radiation therapy.
  * Serum triglyceride level ≤ 300 mg/dL and serum cholesterol ≤ 300 mg/dL.
  * Random or fasting glucose within the upper limits of normal for age. If random glucose is elevated, fasting glucose must be within normal range.
  * SGOT (AST) and SGPT (ALT) ≤3.0 x upper limit of normal for age.

Exclusion Criteria:

* Participant is pregnant or breastfeeding.
* Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
* Participant has a prior history of malignancy, with the exception of non-melanoma skin cancer. Participants with history of skin cancer must have 5 years elapse since that diagnosis, be in remission, and must not have received chemotherapy, immunotherapy, or radiation therapy.