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