Metastatic Ewing's Trial Testing Schedule Enhancement to Improve Outcomes

NCT07194044 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MCC-23281
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 17

Brief Summary

This single arm study is designed to demonstrate the feasibility of a radically different approach for an exceptionally high-risk subset of MES with widely metastatic disease (WMES). We incorporate the use of evolutionary principles that apply to species and population dynamics as related to adaptation and extinction to populations of cancer cells that similarly adapt and that we are attempting to make extinct, resulting in a cure for the patient. Such principles include an initial intense first strike to deplete the bulk of the cancer cells, followed by a series of sequential second strikes towards eliminating residual, resistant populations, followed by a prolonged period of maintenance chemotherapy to eliminate any remnant cells, using agents generally regarded to be active against newly diagnosed ES.

Conditions

Metastatic Ewing Sarcoma

Outcome Measures

Primary Outcomes (2)

• Feasibility and Safety - Consolidation

  The treatment will be considered feasible if 70% of Ewing sarcoma patients make it through consolidation.

  16 months

• Feasibility and Safety - Maintenance

  The treatment will be considered feasible if 50% of Ewing sarcoma patients make it through 6 cycles of maintenance.

  16 months

Secondary Outcomes (3)

• Event-Free Survival

  3 years

• Off Treatment Event Free Survival

  3 years

• Overall Survival

  3 years

Study Arms (1)

Sequential Therapy

EXPERIMENTAL

Weeks 1-8, Vincristine/Doxorubicin/Cyclophosphamide. Weeks 9-14, Irinotecan, Ifosfamide, Vincristine, Actinomycin (IrIVA). Weeks 15-20, Cabozantinib w/ primary site radiation. Weeks 21-26, Topotecan/Cyclophosphamide. Weeks 27-32, High Dose Ifosfamide. Weeks 33-38, Irinotecan/Temozolomide. Maintenance, Weeks 39 up to 104, will consist of alternating 28-day blocks of chemotherapy (Block 1 and Block 2). Oral Cyclophosphamide / Oral Etoposide (Block 1). Vincristine/ Liposomal Doxorubicin (Block 2).

Drug: Vincristine; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Ifosfamide; Drug: Actinomycin; Drug: Irinotecan; Drug: Cabozantinib; Drug: Topotecan; Drug: Temozolomide; Drug: Etoposide; Drug: Liposomal doxorubicin

Interventions

Vincristine DRUG

IV Push

Sequential Therapy

Doxorubicin DRUG

IV

Sequential Therapy

Cyclophosphamide DRUG

IV and Maintenance PO

Sequential Therapy

Ifosfamide DRUG

IV

Sequential Therapy

Actinomycin DRUG

IV

Sequential Therapy

Irinotecan DRUG

IV

Sequential Therapy

Cabozantinib DRUG

PO

Sequential Therapy

Topotecan DRUG

IV

Sequential Therapy

Temozolomide DRUG

IV

Sequential Therapy

Etoposide DRUG

PO

Sequential Therapy

Liposomal doxorubicin DRUG

IV

Sequential Therapy

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be \>1 year of age. There is no upper age limit.
• Patients, in the opinion of the enrolling investigator, must be healthy enough to tolerate protocol therapy.
• Patients must have a new histologic diagnosis of either: widely metastatic Ewing sarcoma or metastatic CIC-rearranged sarcoma.
• Patients must have sufficient tissue submitted (flash frozen tissue, FFPE block, or up to 10 unstained FFPE slides) for correlative testing. This may be from a primary or metastatic site.
• Patients must not have received any prior systemic therapy with the exception that they may have started an initial cycle of vincristine/doxorubicin/cyclophosphamide (VDC) prior to enrollment, i.e. VDC may have been given, but not ifosfamide/etoposide (IE).
• Adequate organ function.
• Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment or abstinence.
• All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.

You may not qualify if:

• Patients with localized disease or lung only metastases for Ewing sarcoma or localized disease for CIC-rearranged sarcomas.
• Patients with central nervous system (CNS) tumors (primary or metastatic) are not eligible.
• Patients who are receiving any other investigational agents for their cancer.
• Patients with a history of cancer that was treated with myelosuppressive chemotherapy or radiation therapy.
• Patients must not be receiving any additional medicines being given for the specific purpose of treating cancer.
• Patients are ineligible if they have uncontrolled intercurrent illness.
• Pregnancy or Breast Feeding: Pregnant or breast-feeding women will not be entered on this study, because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to starting protocol therapy.
• Patients who are considered unable to comply with the safety monitoring requirements of the study are not eligible.

Sponsors & Collaborators

• National Pediatric Cancer Foundation: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (17)

University of Alabama at Birmingham (Children's of Alabama)

Birmingham, Alabama, 35233, United States

RECRUITING

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

NOT YET RECRUITING

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

NOT YET RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Nemours Jacksonville

Jacksonville, Florida, 32207, United States

NOT YET RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536, United States

NOT YET RECRUITING

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

NOT YET RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

NOT YET RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

NOT YET RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

NOT YET RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

NOT YET RECRUITING

Cleveland Clinic Children's

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

NOT YET RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Sarcoma, Ewing

Interventions

Vincristine; Doxorubicin; Cyclophosphamide; Ifosfamide; Dactinomycin; Irinotecan; cabozantinib; Topotecan; Temozolomide; Etoposide; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 3-Ring; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Camptothecin; Dacarbazine; Triazenes; Imidazoles; Azoles; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Matteo Trucco, MD

  Cleveland Clinic Hospital

  PRINCIPAL INVESTIGATOR

• Jonathan Metts, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica Crimella

CONTACT

813-745-6250; Jessica.Crimella@moffitt.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: September 26, 2025
• Study Start: February 5, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

US (17)