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

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.

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

Interventions

PROCEDURE

Biopsy Procedure

Undergo bone marrow aspiration and biopsy

PROCEDURE

Biospecimen Collection

Undergo tissue and/or blood sample collection

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration and biopsy

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow aspiration and biopsy

PROCEDURE

Computed Tomography

Undergo CT

DRUG

Cyclophosphamide

Given IV

DRUG

Doxorubicin Hydrochloride

Given IV

PROCEDURE

Echocardiography Test

Undergo echocardiography

DRUG

Etoposide

Given IV

OTHER

Fludeoxyglucose F-18

Given FDG

DRUG

Ifosfamide

Given IV

DRUG

Irinotecan Hydrochloride

Given IV

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

PROCEDURE

Positron Emission Tomography

Undergo FDG PET

OTHER

Questionnaire Administration

Ancillary studies

RADIATION

Radiation Therapy

Undergo radiation

DRUG

Regorafenib

Given PO

PROCEDURE

Surgical Procedure

Undergo surgery

DRUG

Vincristine Sulfate

Given IV

Sponsors & Collaborators

• Children's Oncology Group

  lead NETWORK

Principal Investigators

• Bhuvana A Setty · Children's Oncology Group

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-11-10

Primary Completion

2027-12-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations