Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma

Inclusion Criteria

• ALT = 16 years of age) OR Lansky PS 50-100% (= = 8 weeks
• Absolute neutrophil count >= 1,000/μL
• NOTE: Patients with tumor metastatic to bone marrow are permitted to receive transfusions to maintain hemoglobin and platelet counts. These patients will not be evaluable for hematologic toxicity. Patients who are refractory to platelet infusions (i.e., unable to maintain platelet counts > 75,000/μL) and have marrow involvement and platelet counts 2 years have elapsed since the initial diagnosis of Ewing sarcoma
• Prior therapy with cyclophosphamide or vincristine is allowed
• Minor surgical procedures (e.g., biopsies) for limited purposes of tissue retrieval allowed
• Minor procedures include indwelling IV catheter placement and needle biopsy for diagnostic purposes
• For minor surgeries, patients should not receive the first planned dose of bevacizumab until the wound is healed and 7 days have elapsed
• At least 6 months since prior craniospinal radiotherapy or radiotherapy to >= 50% of the pelvis
• At least 3 months since prior autologous stem cell transplantation (SCT)
• Platelet count >= 75,000/μL (transfusion independent)
• Hemoglobin >= 8.0 g/dL (may receive RBC transfusions)
• Direct bilirubin = = 70 mL/min OR serum creatinine normal for age
• Hypertension must be well controlled on stable doses of medication for >= 2 weeks prior to enrollment
• Negative pregnancy test
• Female patients who are lactating must agree to stop breast-feeding
• II) The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• Shortening fraction > 28% OR ejection fraction > 50%
• Recovered from any prior surgical procedure
• Sexually active patients of childbearing potential must agree to use effective contraception
• Patients on full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 are eligible if both of these criteria are met:
• I) The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin

Exclusion Criteria

• Radiological or clinical evidence for parenchymal brain metastases or neuro axis involvement
• Documented, chronic nonhealing wound, ulcer, or significant traumatic injury (those with bone fractures, including pathological fractures, or requiring surgical intervention) within the past 28 days
• Other bone complications
• Deep venous thrombosis (including pulmonary embolism) within the past 3 months
• Recent (i.e., within 6 months) arterial thromboembolic events, including transient ischemic attack or cerebrovascular accident
• History of myocardial infarction, severe or unstable angina, or peripheral vascular disease Prior bevacizumab
• Radiotherapy or surgery for local control of recurrent disease concurrently with bevacizumab (bevacizumab must be held if radiotherapy or surgery is required)
• Radiotherapy to localized painful lesions is allowed, provided >= 1 measurable lesion is not irradiated
• Radiotherapy for local metastatic tumor control allowed after the first 2 courses of therapy
• Other cancer chemotherapy or immunomodulating agents
• Steroid use is allowed
• Prior allogeneic SCT