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

Running, not enrolling · Phase 2/Phase 3

Conditions studied: CIC-Rearranged Sarcoma, Metastatic Ewing Sarcoma, Metastatic High Grade Sarcoma, Metastatic Undifferentiated Round Cell Sarcoma, Metastatic Undifferentiated Sarcoma, Not Otherwise Specified, Round Cell Sarcoma With EWSR1-non-ETS Fusion, Sarcoma With BCOR Genetic Alterations

In brief

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.

Key facts

Study ID: NCT06820957
Run by: Children's Oncology Group
People needed: 2
Starts: 2025-11-10
Expected to finish: 2027-07-01
Last updated by the study team: 2026-07-29

Who can join

Age: 12 and older, up to 50. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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 metastatic sites is not required. For this study, distant metastatic disease is defined as one or more of the following:
Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastasis. If there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed
Contralateral pleural effusion and/or contralateral pleural nodules
Distant lymph node involvement
Patients with pulmonary nodules are considered to have metastatic disease if the patient has:
Solitary nodule ≥ 0.5 cm or multiple nodules of ≥ 0.3 cm unless lesion is biopsied and negative for tumor

You may not qualify if…

Patients with regional node involvement as their only site of disease beyond the primary tumor
Patients whose primary tumors arise in the intra-dural soft tissue (e.g., brain and spinal cord)
Note: metastatic disease is allowable
Patients with known Charcot-Marie-Tooth disease
Patients who have had complete or partial resection of the primary tumor at initial diagnosis will only be eligible if adequate imaging (CT or MRI for most primary tumor sites) was obtained prior to surgery
Patients who have received prior chemotherapy for current diagnosis, except for patients who have started cycle 1 VDC post-consent and within the timelines allowed for
Patients who have received prior radiation therapy for current diagnosis
Patients previously treated with a multitargeted tyrosine kinase inhibitor
History of organ allograft (including allogeneic bone marrow transplant)
Known hypersensitivity to regorafenib
Active or chronic hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
Patients receiving strong CYP3A4 inducers or strong CYP3A4 inhibitors
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
Lactating females who plan to breastfeed their infants
Females of childbearing potential must agree to either practice medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse for the duration of the protocol therapy through 12 months after the last dose of cyclophosphamide or ifosfamide, 6 months after the last dose of doxorubicin, etoposide, and irinotecan, and 7 months after the last dose of regorafenib, whichever is longer
Male patients with female partners of childbearing potential must agree to either practice a medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse for the duration of the protocol therapy through 6 months after the last dose of doxorubicin and ifosfamide, 4 months after the last dose of cyclophosphamide, etoposide and regorafenib, and 3 months after the last dose of irinotecan, whichever is longer
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Where it is running

Children's Hospital of Alabama — Birmingham, Alabama, United States
Kapiolani Medical Center for Women and Children — Honolulu, Hawaii, United States
Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
OSF Children's Hospital of Illinois — Peoria, Illinois, United States
NYU Langone Hospital - Long Island — Mineola, New York, United States
Saint Christopher's Hospital for Children — Philadelphia, Pennsylvania, United States
Prisma Health Richland Hospital — Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center — Greenville, South Carolina, United States
East Tennessee Childrens Hospital — Knoxville, Tennessee, United States

Full record on ClinicalTrials.gov

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