Irinotecan, Temozolomide and Bevacizumab in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Newly Diagnosed Patients With Desmoplastic Small Round Cell Tumor

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