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

Conditions

• 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

Eligibility Criteria

Sex

ALL

Age

12 Years - 50 Years

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo bone marrow aspiration and biopsy
• Biospecimen Collection — PROCEDURE
  Undergo tissue and/or blood sample collection
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration and biopsy
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow aspiration and biopsy
• Computed Tomography — PROCEDURE
  Undergo CT
• Cyclophosphamide — DRUG
  Given IV
• Doxorubicin Hydrochloride — DRUG
  Given IV
• Echocardiography Test — PROCEDURE
  Undergo echocardiography
• Etoposide — DRUG
  Given IV
• Fludeoxyglucose F-18 — OTHER
  Given FDG
• Ifosfamide — DRUG
  Given IV
• Irinotecan Hydrochloride — DRUG
  Given IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Positron Emission Tomography — PROCEDURE
  Undergo FDG PET
• Questionnaire Administration — OTHER
  Ancillary studies
• Radiation Therapy — RADIATION
  Undergo radiation
• Regorafenib — DRUG
  Given PO
• Surgical Procedure — PROCEDURE
  Undergo surgery
• Vincristine Sulfate — DRUG
  Given IV

Study Details

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 Dates

Start date

Nov 10, 2025

Status verified

Feb 2026

Primary completion

Dec 31, 2027

Completion

Dec 31, 2027

Study Design

Enrollment

437 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Regimen A (VDC/IE)
  See Detailed description
• Experimental: Regimen B (VIrR/VDC/IE)
  See Detailed Description

Primary Outcome Measure

Time to event-free survival (EFS) post-Consolidation I (C1) [ Time Frame: 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 ]

Locations (9)

Find similar trials in Birmingham, AL

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