Clinical Trial Finder

Inclusion Criteria:

• - 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.

• - Weight/Age: patients must be ≥40 kg at the time of study enrollment, but may be of any age.

• - Diagnosis: Patients must have histologically documented locally advanced or metastatic disease confirmed at 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.

• - Therapeutic options: patient's current disease state must be one which has failed standard cytotoxic chemotherapy including cyclophosphamide/doxorubicin/vincristine and ifosfamide/etoposide.

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

• - Performance level: Karnofsky ≥70% for patients >16 years of age and Lansky ≥70 for patients ≤16 years of age.

• - Prior Therapy: patients may have had any number of 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.

Organ Function Requirements:

• - Adequate bone marrow function defined as: - Absolute neutrophil count (ANC) ≥ 1500/mm3.

• - Platelet count ≥ 100,000/mm3.

• - Hemoglobin ≥ 8 g/dl.

• - Adequate renal function defined as estimated glomerular filtration (eGFR) rate ≥ 60 mL/min/1.73m2: - as estimated by CKD-EPI equation for patients ≥ 18 years of age OR.

• - As estimated by cystatin C for patients < 18 years of age.

• - Adequate liver function defined as: - Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for age.

• - AST or 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.

• - Adequate cardiac function defined as: - Left ventricular ejection fraction (LVEF) >45% as measured on echocardiogram, cardiac MRI, or MUGA.

• - 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 completing study treatment.

Exclusion Criteria:

• - Patients for whom the investigator deems that gemcitabine is not appropriate.

• - Patients who have an uncontrolled infection.

• - Central Nervous System (CNS) Metastases.

• - 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

Arms

Experimental: Ewing sarcoma

Participants have a diagnosis of Ewing sarcoma as molecularly defined by an EWSR1 fusion with an ETS-transcription factor family member including FLI1, ERG, ETV1, ETV4, and FEV

Interventions

Drug: - LY2880070

Patients will receive treatment in 21-day cycles with LY2880070 50 mg twice daily orally on days 2-6, 9-13, and 16-20

Drug: - Gemcitabine

Participants will receive treatment in 21-day cycles with gemcitabine 100 mg/m2 intravenously on days 1, 8 and optionally on day 15