• Consent/Assent: all patients and/or their parents or legally authorized representatives must sign written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

• Age: patients must be ≥12 months of age at the time of study enrollment

• Diagnosis: patients must have histologically documented locally advanced or metastatic desmoplastic small round cell tumor or rhabdomyosarcoma (confirmed at MSK)

• Therapeutic options: patient's current disease state must be one which has failed standard therapy and for which there is no known curative therapy

• Disease Status: patients must have measurable disease based on RECIST 1.1

• Performance level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age

• Prior Therapy: patients may have had any number of prior therapies, but must have recovered from the acute toxic effects of all prior anti-cancer therapy (other than alopecia) as described below and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment

• °patients who have previously received irinotecan and/or temozolomide will be allowed

⁃ 21 days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy

⁃ 7 days must have elapsed after the last dose of anti-cancer agents not known to be myelosuppressive

⁃ 14 days must have elapsed after radiation therapy, and toxicity related to prior radiation therapy must be recovered to grade ≤ 1

⁃ 21 days must have elapsed after the last dose of antibody therapy, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1

• Organ Function Requirements: Adequate bone marrow function defined as:

‣ absolute neutrophil count (ANC) ≥ 1500/mm\^3

⁃ platelet count ≥ 100,000/ mm\^3

⁃ hemoglobin ≥ 8 g/dl

• Adequate renal function defined as:

‣ Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min/1.73m2 OR

⁃ Serum creatinine based on age/gender derived from the Schwartz formula for estimating GFR53

• Adequate liver function defined as:

‣ Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for age

⁃ AST or ALT ≤ 5 x upper limit of normal for patients with liver metastases

⁃ Serum albumin ≥ 2.5 g/dl

• Adequate cardiac function defined as:

‣ echocardiogram with left ventricular ejection fraction (LVEF) \>45%

⁃ QTc \< 470 ms on screening 12 lead electrocardiogram

• Pregnancy/Contraception

‣ post-menarchal females must have a negative urine or serum pregnancy test at screening and ≤ 24 hours prior to study treatment

⁃ males or females of reproductive potential must be willing to use a barrier method of contraception throughout the course of the study and for 6 months after participation