Prexasertib and Irinotecan for the Treatment of Relapsed or Refractory Desmoplastic Small Round Cell Tumor or Rhabdomyosarcoma

Inclusion Criteria

• 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
• Patients must be >= 12 months of age at the time of study enrollment
• Patients must have histologically documented locally advanced or metastatic desmoplastic small round cell tumor or rhabdomyosarcoma (confirmed at Memorial Sloan Kettering [MSK])
• Patient’s current disease state must be one which has failed standard therapy and for which there is no known curative therapy
• Patients must have measurable disease based on RECIST 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
• 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
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000/ mm^3
• Hemoglobin >= 8 g/dl
• Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows: * Age (years): Maximum serum creatinine (mg/dL) * 1 to < 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) * 2 to < 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) * 6 to < 10 years: 1 mg/dL (male); 1 mg/dL (female) * 10 to < 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) * 13 to < 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female) * >= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal for age
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 5 x upper limit of normal for patients with liver metastases
• Serum albumin >= 2.5 g/dl
• Echocardiogram with left ventricular ejection fraction (LVEF) > 45%
• Corrected QT (QTc) < 470 ms on screening 12 lead electrocardiogram
• 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

Exclusion Criteria

• Patients for whom the investigator deems that irinotecan and temozolomide are not appropriate are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who are pregnant or breast feeding are not eligible
• Patients who have a history of torsades de pointes, carry a diagnosis of congestive heart failure, or have a family history of prolonged QT syndrome are not eligible.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with known hypersensitivity to irinotecan or its excipients are not eligible