Recruiting

Phase 1

Sequential StrikesMetastatic Ewing's Trial Testing Schedule Enhancement to Improve Outcomes

Sponsor:

H. Lee Moffitt Cancer Center and Research Institute

Code:

NCT07194044

Conditions

Metastatic Ewing Sarcoma

Eligibility Criteria

Sex: All

Age: 1+

Healthy Volunteers: Not accepted

Interventions

Vincristine

Doxorubicin

Cyclophosphamide

Ifosfamide

Actinomycin

Study Details

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

Study ID

NCT07194044

Start date

Feb 5, 2026

Status verified date

Aug, 2026

Completion date

Oct, 2030

Anticipated

Primary completion date

Oct, 2030

Anticipated

Eligibility Criteria

Sex: All

Age: 1+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Design

Enrollment

15 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Sequential Therapy

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).

Interventions

Vincristine

IV Push

Doxorubicin

Cyclophosphamide

IV and Maintenance PO

Ifosfamide

Actinomycin

Irinotecan

Cabozantinib

Topotecan

Temozolomide

Etoposide

Liposomal doxorubicin

Primary outcome measure

Feasibility and Safety - Consolidation [ Time Frame: 16 months ]
Feasibility and Safety - Maintenance [ Time Frame: 16 months ]

Central Contacts and Locations

Central contacts

Jessica Crimella

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

Locations

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

Recruiting

Birmingham, Alabama, United States, 35233

Principal Investigator:

Elizabeth Alva, MD

Phoenix Children's Hospital

Recruiting

Phoenix, Arizona, United States, 85016

Principal Investigator:

Mona Nourani, DO

University of Florida

Recruiting

Gainesville, Florida, United States, 32610

Principal Investigator:

Joanne Lagmay, MD

University of Miami

Recruiting

Miami, Florida, United States, 33136

Contacts

Eva Pavicic

305-585-5635 EPavicic@med.miami.edu

Principal Investigator:

Aditi Dhir, MD

Johns Hopkins All Children's Hospital

Recruiting

St. Petersburg, Florida, United States, 33701

Principal Investigator:

Blake Foxworthy, MD

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Principal Investigator:

Jonathan Metts, MD

Montefiore Medical Center

Recruiting

The Bronx, New York, United States, 10467

Principal Investigator:

Alice Lee, MD

Duke University Medical Center- Children's Health Center

Recruiting

Durham, North Carolina, United States, 27710

Principal Investigator:

Jessica Sun, MD

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205

Principal Investigator:

Bhuvana Setty, MD

Monroe Carell Jr. Children's Hospital at Vanderbilt

Recruiting

Nashville, Tennessee, United States, 37232

Principal Investigator:

Scott Borinstein, MD, PhD

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Principal Investigator:

Scott Borinstein, MD

Primary Children's Hospital

Recruiting

Salt Lake City, Utah, United States, 84113

Principal Investigator:

Matthew Dietz, DO

More Information

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by H. Lee Moffitt Cancer Center and Research Institute on 2026-08-28.