Irinotecan and Temozolomide in Combination With Existing High Dose Alkylator Based Chemotherapy for Treatment of Patients With Newly Diagnosed Ewing Sarcoma

Inclusion criteria

• Age greater than or equal to one year and less than or equal to 40 years at the time of diagnosis
• Newly diagnosed, previously untreated patients with histologically or molecularly confirmed Ewing sarcoma
• Adequate hematologic function:
• Absolute neutrophil count ≥ 1,000/K/mcl
• Platelet count ≥ 100,000/Kmcl
• Adequate renal function:
• Normal creatinine for age (See table below) OR
• Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 Age(Years) Maximum Serum Creatinine (mg/dL) ≤ 5 0.8 6 to ≤ 10 1 11 to ≤ 15 1.2 ≥ 16 1.5

Adequate hepatic function:

• Total bilirubin ≤ 1.5 x the ULN
• AST ≤ 2.5 x the ULN [in the absence of hepatic involvement of tumor. Patients with hepatic involvement are considered eligibile for study]
• ALT ≤ 2.5 x the ULN [in the absence of hepatic involvement of tumor. Patients with hepatic involvement are considered eligibile for study]

Normal cardiac function:

• Shortening fraction ≥ 28% by echocardiogram OR
• Left ventricular ejection fraction (LVEF) ≥ 50% on technetium- 99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram
• 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 (other than limited, emergent radiotherapy for treatment of eg. spinal cord compromise or threatened airway)
• Pregnant or breastfeeding females