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.
Brief Title
Metastatic Ewing's Trial Testing Schedule Enhancement to Improve Outcomes
Central Contacts
Central Contact Role
Contact
Central Contact Phone
813-745-6250
Central Contact Email
Jessica.Crimella@moffitt.org
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Ewing Sarcoma
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
1 Year
NCT Id
NCT07194044
Org Class
Other
Org Full Name
H. Lee Moffitt Cancer Center and Research Institute
Org Study Id
MCC-23281
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Metastatic Ewing's Trial Testing Schedule Enhancement to Improve Outcomes
Primary Outcomes
Outcome Description
The treatment will be considered feasible if 70% of Ewing sarcoma patients make it through consolidation.
Outcome Measure
Feasibility and Safety - Consolidation
Outcome Time Frame
16 months
Outcome Description
The treatment will be considered feasible if 50% of Ewing sarcoma patients make it through 6 cycles of maintenance.
Outcome Measure
Feasibility and Safety - Maintenance
Outcome Time Frame
16 months
Secondary Outcomes
Outcome Description
EFS is defined as time from treatment initiation to event which includes (1) recurrence, (2) secondary malignancy, and (3) death due to any cause.
Outcome Time Frame
3 years
Outcome Measure
Event-Free Survival
Outcome Description
otEFS is defined as time from treatment initiation to event 66 which includes (1) any recurrence (local or regional, or distant) that leads to coming off protocol therapy and (2) death due to any cause.
Outcome Time Frame
3 years
Outcome Measure
Off Treatment Event Free Survival
Outcome Description
The time to event endpoint of overall survival is defined as the duration of time from diagnosis to death or last follow-up timepoint, where event would be death from any cause.
Outcome Time Frame
3 years
Outcome Measure
Overall Survival
Start Date
Start Date Type
Estimated
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
1
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alice Lee
Investigator Email
alee5@montefiore.org
Investigator Department
Pediatrics
Investigator Division
Pediatric Hematology-Oncology
Investigator Sponsor Organization
External
Study Department
Pediatrics
Study Division
Pediatrics Hematology/Oncology
Categories Mesh Debug
Sarcomas --- OSTEOSARCOMA
Brain, Spine & Nerve Cancers --- NEOPLASMS, CONNECTIVE AND SOFT TISSUE
Cancer --- NEOPLASMS
Cancer --- SARCOMA
Sarcomas --- SARCOMA
MeSH Terms
SARCOMA, EWING
OSTEOSARCOMA
NEOPLASMS, BONE TISSUE
NEOPLASMS, CONNECTIVE TISSUE
NEOPLASMS, CONNECTIVE AND SOFT TISSUE
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
SARCOMA
VINCRISTINE
DOXORUBICIN
CYCLOPHOSPHAMIDE
IFOSFAMIDE
DACTINOMYCIN
IRINOTECAN
CABOZANTINIB
TOPOTECAN
TEMOZOLOMIDE
ETOPOSIDE
LIPOSOMAL DOXORUBICIN
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