Active — Not RecruitingPhase 2/3

Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body

United States437 participantsStarted 2025-11-10

Plain-language summary

This phase II/III trial compares the effect of vincristine, irinotecan, and regorafenib (VIrR) in combination with vincristine, doxorubicin, cyclophosphamide (VDC), ifosfamide and etoposide (IE) to usual treatment with VDC/IE for the treatment of newly diagnosed Ewing sarcoma or other round cell sarcomas that have spread from where they first started (primary site) to other places in the body (metastatic). Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Regorafenib, a type of kinase inhibitor and a type of antiangiogenesis agent, blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill tumor cells. It also blocks a certain enzyme needed for cell division and DNA repair. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells. It may also lower the body's immune response. Ifosfamide, a type of alkylating agent and a type of antimetabolite, attaches to DNA in cells and may kill tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Giving VIrR/VDC/IE may be more effective than usual treatment with VDC/IE in treating patients with newly diagnosed metastatic Ewing sarcoma or other round cell sarcomas.

Who can participate

Age range12 Years – 50 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * All patients must be enrolled on APEC14B1 and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on AEWS2431 * Patients must be ≥ 12 months to ≤ 50 years of age at time of enrollment * Newly diagnosed Ewing sarcoma and other round cell sarcomas as follows. For the purposes of eligibility, the following pathology diagnoses are eligible and molecular confirmation is not required to enroll: * Histologically confirmed Ewing sarcoma * Suspected Ewing sarcoma with molecular confirmation pending * Suspected high grade round cell sarcomas/sarcomas with eligible molecular alterations, pending molecular confirmation * Round cell sarcoma consistent with Ewing sarcoma * Round cell sarcoma not otherwise specified * Round cell sarcoma * Round cell sarcomas with EWSR1-non-ETS fusion * CIC-rearranged sarcoma * Sarcoma with BCOR genetic alterations * Patients with the following pathologic diagnoses that are known to contain EWSR1 or FUS fusions are not eligible: * Angiomatoid fibrous histiocytoma * Extraskeletal myxoid chondrosarcoma * Desmoplastic small round cell tumor * Clear cell sarcoma * Myxoid liposarcoma * If clinical molecular testing that reports both fusion partners has been successfully completed by the site prior to enrollment, patients may only enroll if that testing reported one of the eligible fusions * All patients must have evidence of distant metastatic disease. Biopsy of met…

What they're measuring

Time to event-free survival (EFS) post-Consolidation I (C1)

Timeframe: From randomization to progression or relapse, diagnosis of a second malignant neoplasm, death, or last patient contact, whichever occurs first, assessed up to 10 years

Trial details

NCT IDNCT06820957

SponsorChildren's Oncology Group

Sponsor typeNETWORK

Study typeINTERVENTIONAL

Primary completion2027-12-31