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

This study adds irinotecan, temozolomide and bevacizumab to the chemotherapy regimen currently used to treat Desmoplastic small round cell tumor (DSRCT). The investigators are doing this study to find out what effects, good and/or bad, the combination of irinotecan, temozolomide and bevacizumab has on the patient and the DSRCT cancer.


Eligibility Criteria:
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