Inclusion Criteria:
- Age greater than or equal to 1 year, less than 30 years
- Newly diagnosed, previously untreated patients with histologically or molecularly confirmed DSRCT
- Adequate hematologic function:
- Absolute neutrophil count ≥ 1,000/mm3
- Platelet count ≥ 100,000/mytm3
- Adequate renal function:
- Normal creatinine for age OR
- Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2
- Adequate hepatic function:
- Total bilirubin ≤ 1.5 x the ULN for age
- AST ≤ 2.5 x the ULN for age [in the absence of hepatic involvement of tumor]
- Normal cardiac function
- Shortening fraction greater than or equal to 28% by echocardiogram OR
- Left ventricular ejection fraction (LVEF) greater than or equal to 50% on technetium-99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram
- Hypertension must be well controlled on stable doses of medication for at least two weeks prior to enrollment.
- Patients must consent to an indwelling central venous catheter.
- Sexually active patients of reproductive potential must be willing to use an effective method of contraception.
Exclusion Criteria:
- Prior chemotherapy or radiotherapy
- Pregnant or breastfeeding females
- Patients with documented chronic non-healing wound, ulcer or bone fracture.
- Incomplete healing from previous oncologic or other major surgery.
- Surgical procedures:
Patients who have undergone major surgery (including open biopsy, thoracotomy, organ resection, exploratory laparotomy, arteriovenous grafts) <28 days prior to enrollment will have bevacizumab dosing delayed as outlined in section 9.1
- Patients must be at least 48 hours from placement of central catheter before receiving first dose of bevacizumab
- Minor surgical procedures (needle/laparoscopic core biopsies) for limited purposes of tissue retrieval will be allowed. Patients should not receive the first planned dose of bevacizumab until the wound is healed and 7 days have elapsed since the procedure.
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- Thrombosis:
- Patients must not have had a deep venous or arterial thrombosis (non-central venous catheter related) within the last three months prior to study entry.
- Patients with cerebrovascular accident or transient ischemic attack within 6 months of therapy are excluded
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry.
- CNS status: Patients must not have known CNS metastases or leptomeningeal disease.
Screening with brain imaging is not required for asymptomatic patients. Proteinuria: Urine protein: creatinine ratio greater than or equal to 1.0
- Uncontrolled hypertension (defined as SBP and/or DBP > 95th percentile for age)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- NYHA Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 12 months prior to Day 1
- History of stroke or transient ischemic attack
- Significant vascular (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
- Known hypersensitivity to any component of bevacizumab