a study of ly2880070 and gemcitabine in people with ewing sarcoma,ewing-like sarcoma, and desmoplastic small round cell tumor

Conditions: Ewing Sarcoma; Ewing-Like Sarcoma

Summary: the purpose of this study is to find out whether ly2880070 combined with the chemotherapy drug gemcitabine is an effective treatment for ewing sarcoma or ewing-like sarcoma.


Eligibility criteria:
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

Keywords: ewing sarcoma ewing-like sarcoma ly2880070 gemcitabine 21-428 memorial sloan kettering cancer center