This study investigates the effectiveness of combination chemotherapy with or without an investigational medication in treating patients with Ewing sarcoma that has spread to other parts of the body. Ewing sarcoma is a type of cancer that forms in bone or soft tissue. The purpose of this study is to understand if adding the investigational medication improves event-free survival, which means the time patients live without the cancer getting worse.

Participants in this study will receive either multiagent chemotherapy alone or with an investigational medication. Chemotherapy is a treatment that uses powerful drugs to kill cancer cells or stop them from growing. The investigational medication is being tested to see if it can improve the effectiveness of the chemotherapy. Participants will be closely monitored throughout the study to assess treatment effects and any side effects.

• Who can participate: Patients eligible for this study must have a diagnosis of Ewing sarcoma or peripheral primitive neuroectodermal tumor with metastatic disease in areas such as the lung, bone, or bone marrow. They should not have received prior chemotherapy or radiation therapy, must agree to use effective contraception if of reproductive potential, and should not have pre-existing diabetes mellitus or be receiving chronic pharmacologic doses of corticosteroids.
• Study details: Participants will be assigned to receive either chemotherapy alone or with an investigational medication. The investigational medication is being tested and is not yet approved. A placebo is not used in this study. Participants will need to undergo regular monitoring to track the treatment's effects and any side effects.