A Study of LY2880070 and Gemcitabine in People with Locally Advanced or Metastatic Ewing Sarcoma, Ewing-Like Sarcoma, or Desmoplastic Small Round Cell Tumor

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 >= 40 kg at the time of study enrollment, but may be of any age
• Patients must have histologically documented locally advanced or metastatic disease confirmed at Memorial Sloan Kettering (MSK) as follows: * Main cohort: Ewing sarcoma as molecularly defined by an EWSR1 fusion with an ETS-transcription factor family member including FLI1, ERG, ETV1, ETV4, and FEV * Pilot cohort: Ewing-like sarcomas including CIC-rearranged sarcoma, BCOR-rearranged sarcoma, and sarcomas with a rearrangement between EWSR1 and a non-ETS family gene or desmoplastic small round cell tumor as molecularly defined by an EWSR1-WT1 fusion ** Note: Any patient being enrolled into the pilot cohort that does not have a CIC, BCOR- rearranged sarcoma, or desmoplastic small round cell tumor will be reviewed with study pathologist, Dr. Cristina Antonescu, to ensure the categorization as Ewing-like sarcoma is appropriate
• Patients must be able to swallow capsules
• Patient’s current disease state must be one which has failed standard cytotoxic chemotherapy including cyclophosphamide/doxorubicin/vincristine and ifosfamide/etoposide
• Patients must have measurable disease based on RECIST 1.1
• Karnofsky >= 70% for patients >16 years of age and Lansky >= 70 for patients =< 16 years of age
• Patients may have had any number of prior regimens and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment * Note: Patients who have previously received gemcitabine will be allowed unless they had hypersensitivity or unacceptable toxicity attributed to gemcitabine ** >= 21 days must have elapsed after the last dose of cytotoxic or myelosuppressive chemotherapy and patients must have recovered from the acute toxic effects of these agents (other than alopecia) ** >= 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
• Estimated glomerular filtration (eGFR) rate >= 60 mL/min/1.73m^2: * As estimated by Chronic Kidney Disease Epidemiology (CKD-EPI) equation for patients >= 18 years of age OR * As estimated by cystatin C for patients < 18 years of age
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal for age
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal for patients without liver metastases
• AST or ALT =< 5 x upper limit of normal for patients with liver metastases
• Serum albumin >= 2.5 g/dl
• Left ventricular ejection fraction (LVEF) > 45% as measured on echocardiogram, cardiac magnetic resonance imaging (MRI), or multigated acquisition (MUGA)
• 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 completing study treatment

Exclusion Criteria

• Patients for whom the investigator deems that gemcitabine is not appropriate
• Patients who have an uncontrolled infection
• Patients who have symptomatic central nervous system (CNS) metastases. Note: patients with treated and asymptomatic CNS metastases are eligible
• Patients with CNS metastases requiring corticosteroids for management
• If the treatment of CNS disease requires anticonvulsants, the dose must have been stable for >= 4 weeks
• Patients who are pregnant or breast feeding
• 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
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• Patients with known hypersensitivity to gemcitabine