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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 1 Year
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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).
  • Drug: Vincristine
    IV Push
  • Drug: Doxorubicin
    IV
  • Drug: Cyclophosphamide
    IV and Maintenance PO
  • Drug: Ifosfamide
    IV
  • Drug: Actinomycin
    IV
  • Drug: Irinotecan
    IV
  • Drug: Cabozantinib
    PO
  • Drug: Topotecan
    IV
  • Drug: Temozolomide
    IV
  • Drug: Etoposide
    PO
  • Drug: Liposomal doxorubicin
    IV

Recruiting Locations

University of Alabama at Birmingham (Children's of Alabama)
Birmingham 4049979, Alabama 4829764 35233

More Details

Status
Recruiting
Sponsor
H. Lee Moffitt Cancer Center and Research Institute

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.