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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 |
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Weight/Age: patients must be ≥40 kg at the time of study enrollment, but may be of any age |
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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 |
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Note: Any patient being enrolled into the pilot cohort will be reviewed with study |
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pathologist, Dr. Cristina Antonescu, to ensure the categorization as Ewing-like sarcoma is |
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appropriate |
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Patients must be able to swallow capsules |
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Therapeutic options: patient's current disease state must be one which has failed |
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standard cytotoxic chemotherapy including cyclophosphamide/doxorubicin/vincristine and |
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ifosfamide/etoposide |
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Disease Status: patients must have measurable disease based on RECIST 1.1 |
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Performance level: Karnofsky ≥70% for patients >16 years of age and Lansky ≥70 for |
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patients ≤16 years of age |
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Prior Therapy: patients may have had no more than 4 prior regimens (including |
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frontline therapy) and must meet the following minimum duration from prior anti-cancer |
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directed therapy prior to enrollment |
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Note: Patients who have previously received gemcitabine will be allowed unless they had |
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hypersensitivity or unacceptable toxicity attributed to gemcitabine |
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≥ 21 days must have elapsed after the last dose of cytotoxic or myelosuppressive |
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chemotherapy and patients must have recovered from the acute toxic effects of these |
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agents (other than alopecia) |
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≥ 14 days must have elapsed after radiation therapy, and toxicity related to prior |
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radiation therapy must be recovered to grade ≤ 1 |
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≥ 21 days must have elapsed after the last dose of antibody therapy, and toxicity |
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related to prior antibody therapy must be recovered to grade ≤ 1 |
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Organ Function Requirements |
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Adequate bone marrow function defined as |
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Absolute neutrophil count (ANC) ≥ 1500/mm3 |
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Platelet count ≥ 100,000/mm3 |
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Hemoglobin ≥ 8 g/dl |
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Adequate renal function defined as estimated glomerular filtration (eGFR) rate ≥ 60 |
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mL/min/1.73m2 |
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as estimated by CKD-EPI equation for patients ≥ 18 years of age OR |
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As estimated by cystatin C for patients < 18 years of age |
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Adequate liver function defined as |
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Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for |
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age |
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AST or ALT ≤ 2.5 x upper limit of normal for patients without liver metastases |
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AST or ALT ≤ 5 x upper limit of normal for patients with liver metastases |
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Serum albumin ≥ 2.5 g/dl |
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Adequate cardiac function defined as |
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Left ventricular ejection fraction (LVEF) >45% as measured on echocardiogram |
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cardiac MRI, or MUGA |
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QTc < 470 ms on screening 12 lead electrocardiogram |
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Pregnancy/Contraception |
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Post-menarchal females must have a negative urine or serum pregnancy test at |
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screening and ≤ 24 hours prior to study treatment |
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Males or females of reproductive potential must be willing to use a barrier |
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method of contraception throughout the course of the study and for 6 months after |
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completing study treatment |
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Patients for whom the investigator deems that gemcitabine is not appropriate
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Patients who have an uncontrolled infection
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Central Nervous System (CNS) Metastases
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Patients who have symptomatic central nervous system (CNS) metastases. Note
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patients with treated and asymptomatic CNS metastases are eligible
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Patients with CNS metastases requiring corticosteroids for management
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If the treatment of CNS disease requires anticonvulsants, the dose must have been
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stable for ≥ 4 weeks
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Patients who are pregnant or breast feeding
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Patients who have a history of Torsades de Pointes, carry a diagnosis of congestive
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heart failure, or have a family history of prolonged QT syndrome
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Patients who, in the opinion of the investigator, may not be able to comply with the
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safety monitoring requirements of the study
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Patients with known hypersensitivity to gemcitabine
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