Inclusion
Relapsed: Participants that have achieved CR at any point and then relapsed following/during standard of care therapy.
Refractory: Participants that failed to achieve CR after standard of care therapy or having progressed during standard of care therapy.
Note: Standard of care therapy for Ewing sarcoma includes multi-agent chemotherapy with local control consisting of either surgery and/or radiation therapy. 3. Extent of disease is judged by treating team to be amenable to the delivery of definitive local control (either definitive radiation, surgery, or a combination of these) at the time of study enrollment (to be completed after protocol defined Cycle 2). 4. Participants may enroll anytime during Cycle 1 or 2, prior to local control, as long as they received the same treatment during Cycle 1 and 2 as prescribed in this protocol. 5. Relapsed or refractory disease, including at least one of the following:
Tumor by CT or MRI
FDG-PET that is positive for disease
Bone Marrow biopsy/aspirate that is positive for disease
For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr)
OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2 7. Adequate liver function defined as:
Age
Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases. If there is any doubt whether lesions are metastatic, a biopsy of those lesions should be performed.
Contralateral pleural effusion and/or contralateral pleural nodules.
Distant lymph node involvement.
Participants with pulmonary nodules are considered to have metastatic disease if the participant has:
Solitary nodule ≥0.5 cm or multiple nodules of ≥0.3 cm unless lesion is biopsied and negative for tumor;
Participants with solitary nodule \<0.5 cm or multiple nodules \<0.3 cm are not considered to have lung metastasis unless biopsy documents tumor.
Bone marrow metastatic disease is based on morphologic evidence of Ewing sarcoma based on H\&E stains. In the absence of morphologic evidence of marrow involvement on H\&E, participants with bone marrow involvement detected ONLY by flow cytometry, RT PCR, FISH, or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study.
For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr)
OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2 5. Adequate liver function defined as:
Total bilirubin ≤1.5 x upper limit of normal (ULN) for age, and
SGPT (ALT \<3 x upper limit of normal (ULN) for age (except for participants with liver metastasis who may enroll if ALT \< 5 times ULN for age). 6. Adequate cardiac function defined as:
Shortening fraction of ≥27% or
Ejection fraction of ≥50% 7. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy. 8. Participants must have a Lansky Play Scale or Karnofsky Performance Scale score of ≥ 60. 9. Participants of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding. 10. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).
Age
Surgical resection of all possible sites of suspected pulmonary metastases in order to achieve a complete remission within 4 weeks prior to study enrollment\*
Pathologic confirmation of metastases from at least one of the resected sites.
No local recurrence or metastatic disease elsewhere. \*For participants with bilateral pulmonary metastases, resection must be performed from both lungs and the study enrollment must be within 4 weeks from date of the last lung surgery. No evidence of pulmonary metastatic disease; participants may have no visible lung nodules greater than 3 mm, and not considered to be disease.
Myelosuppressive anti-cancer therapy: Must not have been received within 2 weeks of study entry (4 weeks if prior nitrosourea).
Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.
Radiation therapy (RT): ≥2 weeks for local palliative RT (small port); ≥6 weeks must have elapsed if prior craniospinal RT or if ≥50% radiation of pelvis; ≥6 weeks must have elapsed if other substantial BM radiation.
Surgery: ≥2 weeks from last major surgery, including pulmonary metastasectomy, with the exclusion of a central line placement and core needle or small open biopsies.
Platelet count ≥50,000/μL without transfusion in last 7 days
Hgb ≥8.5 without transfusion in last 7 days 7. Adequate renal function defined as:
For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr)
OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2 8. Adequate liver function defined as:
Total bilirubin ≤1.5 x upper limit of normal (ULN) for age.
SGPT (ALT \<3 x upper limit of normal (ULN) for age. 9. Adequate cardiac function defined as:
Shortening fraction of ≥27%, or
Ejection fraction of ≥50%. 10. Adequate pulmonary function defined as:
For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr
For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr)
OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2 12. Adequate cardiac function defined as:
Shortening fraction of ≥28%, or
Ejection fraction of ≥50% 13. Adequate liver function defined as:
Total bilirubin ≤1.5 x upper limit of normal (ULN) for age
SGPT (ALT \<3 x upper limit of normal (ULN) for age. 14. Participants must have fully recovered from the hematological and bone marrow suppression effects of prior chemotherapy. 15. Participants of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Participants who are lactating must agree to stop breast-feeding. 16. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).