Ignite Creation Date:
2025-12-24 @ 6:41 PM
Ignite Modification Date:
2025-12-24 @ 6:41 PM
Study NCT ID:
NCT06820957
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-24
First Post:
2025-02-06
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
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
Sponsor:
Children's Oncology Group
Organization:
Study Overview
Official Title:
Randomized Phase 2/3 Trial of Vincristine-Irinotecan-Regorafenib in Combination With Vincristine-Doxorubicin-Cyclophosphamide (VDC) and Ifosfamide-Etoposide (IE) in Patients With Newly Diagnosed Metastatic Ewing Sarcoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine if the event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma is improved when treated with vincristine-irinotecan-regorafenib (VIrR) after initial treatment with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) compared to patients treated with 17 cycles of interval compressed VDC and IE chemotherapy.
SECONDARY OBJECTIVES:
I. To compare the overall survival (OS) of patients with newly diagnosed metastatic Ewing sarcoma treated with VDC/IE/VIrR versus VDC/IE.
II. To compare the toxicity profile of VDC/IE/VIrR to VDC/IE in patients with newly diagnosed metastatic Ewing sarcoma, using both investigator-reported and patient-reported Common Terminology Criteria for Adverse Events (CTCAE).
III. To describe the feasibility and toxicity of augmented dose radiotherapy with 64.8 Gy as local control for patients with newly diagnosed metastatic Ewing sarcoma with large primary tumors.
IV. To prospectively validate that circulating tumor-derived DNA (ctDNA) levels greater than or equal to 5% at the time of diagnosis are associated with increased risk of EFS-event for patients with newly diagnosed metastatic Ewing sarcoma.
V. To prospectively validate that elevated ctDNA levels greater than or equal to 0.5% burden following one cycle of chemotherapy are associated with increased risk of EFS-event for patients with newly diagnosed metastatic Ewing sarcoma.
EXPLORATORY OBJECTIVES:
I. To estimate 1- and 2-year EFS and response rate for patients with newly diagnosed, eligible metastatic round cell sarcomas other than Ewing sarcoma.
II. To characterize the change in fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) imaging response of primary disease site at the end of Induction chemotherapy and its association with EFS.
III. To explore distinguishing histologic attributes of Ewing sarcoma and round cell sarcomas that mimic Ewing sarcoma.
IV. To collect bone marrow and tissue samples to bank for future research. V. To explore other ctDNA predictor variables, time points, and potential association with EFS in patients with newly diagnosed metastatic Ewing sarcoma.
VI. To estimate the frequency of selected toxicities by Patient Reported Outcomes (PRO)-CTCAE and symptom bother by Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) and to evaluate if these findings are associated with duration of protocol therapy and treatment arm.
OUTLINE:
INDUCTION: Patients receive vincristine intravenously (IV) on days 1 and 8, doxorubicin IV over 3-15 minutes on days 1 and 2, and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 3 and 5. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of cycles 2, 4 and 6. Cycles repeat every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery or radiation therapy per investigator choice.
CONSOLIDATION I: Patients receive vincristine IV on days 1 and 8, doxorubicin IV over 3-15 minutes on days 1 and 2, and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1 and 2. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of cycles 3 and 4. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION II: After 10 cycles of therapy, patients with Ewing Sarcoma are randomized to 1 of 2 regimens. Patients with a diagnosis of other eligible metastatic round cell sarcomas are assigned to Regimen A.
REGIMEN A: Patients receive vincristine IV on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 3, 5 and 7. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of cycles 2, 4 and 6. Cycles repeat every 14 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. After systemic therapy completed, patients undergo metastatic site radiation therapy.
REGIMEN B: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 90 minutes on days 1-5 of each cycle. Patients also receive regorafenib orally (PO) on days 8-14 or 15-21 of cycle 1, and then on days 8-21 of cycles thereafter. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After systemic therapy completed, patients undergo metastatic site radiation therapy.
Additionally, patients undergo blood sample collection, echocardiography, magnetic resonance imaging (MRI), computed tomography (CT), chest CT, and/or FDG-PET throughout the study. Patients may also undergo optional collection of tumor tissue and/or bone marrow aspiration and biopsy on study.
After completion of study treatment, patients are followed every 3 months for years 1 and 2, every 6 months for years 3 and 4 then every 12 months for years 5-10.
I. To determine if the event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma is improved when treated with vincristine-irinotecan-regorafenib (VIrR) after initial treatment with vincristine-doxorubicin-cyclophosphamide (VDC) and ifosfamide-etoposide (IE) compared to patients treated with 17 cycles of interval compressed VDC and IE chemotherapy.
SECONDARY OBJECTIVES:
I. To compare the overall survival (OS) of patients with newly diagnosed metastatic Ewing sarcoma treated with VDC/IE/VIrR versus VDC/IE.
II. To compare the toxicity profile of VDC/IE/VIrR to VDC/IE in patients with newly diagnosed metastatic Ewing sarcoma, using both investigator-reported and patient-reported Common Terminology Criteria for Adverse Events (CTCAE).
III. To describe the feasibility and toxicity of augmented dose radiotherapy with 64.8 Gy as local control for patients with newly diagnosed metastatic Ewing sarcoma with large primary tumors.
IV. To prospectively validate that circulating tumor-derived DNA (ctDNA) levels greater than or equal to 5% at the time of diagnosis are associated with increased risk of EFS-event for patients with newly diagnosed metastatic Ewing sarcoma.
V. To prospectively validate that elevated ctDNA levels greater than or equal to 0.5% burden following one cycle of chemotherapy are associated with increased risk of EFS-event for patients with newly diagnosed metastatic Ewing sarcoma.
EXPLORATORY OBJECTIVES:
I. To estimate 1- and 2-year EFS and response rate for patients with newly diagnosed, eligible metastatic round cell sarcomas other than Ewing sarcoma.
II. To characterize the change in fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) imaging response of primary disease site at the end of Induction chemotherapy and its association with EFS.
III. To explore distinguishing histologic attributes of Ewing sarcoma and round cell sarcomas that mimic Ewing sarcoma.
IV. To collect bone marrow and tissue samples to bank for future research. V. To explore other ctDNA predictor variables, time points, and potential association with EFS in patients with newly diagnosed metastatic Ewing sarcoma.
VI. To estimate the frequency of selected toxicities by Patient Reported Outcomes (PRO)-CTCAE and symptom bother by Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) and to evaluate if these findings are associated with duration of protocol therapy and treatment arm.
OUTLINE:
INDUCTION: Patients receive vincristine intravenously (IV) on days 1 and 8, doxorubicin IV over 3-15 minutes on days 1 and 2, and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 3 and 5. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of cycles 2, 4 and 6. Cycles repeat every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery or radiation therapy per investigator choice.
CONSOLIDATION I: Patients receive vincristine IV on days 1 and 8, doxorubicin IV over 3-15 minutes on days 1 and 2, and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1 and 2. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of cycles 3 and 4. Cycles repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION II: After 10 cycles of therapy, patients with Ewing Sarcoma are randomized to 1 of 2 regimens. Patients with a diagnosis of other eligible metastatic round cell sarcomas are assigned to Regimen A.
REGIMEN A: Patients receive vincristine IV on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1 of cycles 1, 3, 5 and 7. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of cycles 2, 4 and 6. Cycles repeat every 14 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. After systemic therapy completed, patients undergo metastatic site radiation therapy.
REGIMEN B: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 90 minutes on days 1-5 of each cycle. Patients also receive regorafenib orally (PO) on days 8-14 or 15-21 of cycle 1, and then on days 8-21 of cycles thereafter. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After systemic therapy completed, patients undergo metastatic site radiation therapy.
Additionally, patients undergo blood sample collection, echocardiography, magnetic resonance imaging (MRI), computed tomography (CT), chest CT, and/or FDG-PET throughout the study. Patients may also undergo optional collection of tumor tissue and/or bone marrow aspiration and biopsy on study.
After completion of study treatment, patients are followed every 3 months for years 1 and 2, every 6 months for years 3 and 4 then every 12 months for years 5-10.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2025-00801 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| AEWS2431 | OTHER | Children's Oncology Group | View | |
| AEWS2431 | OTHER | CTEP | View | |
| U10CA180886 | NIH | None | https://reporter.nih.gov/quic… | View |