A Study of LY2880070 and Gemcitabine in People With Ewing Sarcoma,Ewing-Like Sarcoma, and Desmoplastic Small Round Cell Tumor
Ewing Sarcoma, Ewing-Like Sarcoma
About this trial
This is an interventional treatment trial for Ewing Sarcoma focused on measuring Ewing Sarcoma, Ewing-Like Sarcoma, LY2880070, Gemcitabine, 21-428, Memorial Sloan Kettering Cancer Center
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
Note: Any patient being enrolled into the pilot cohort 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 no more than 4 prior regimens (including frontline therapy) 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
Sites / Locations
- Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
Arms of the Study
Arm 1
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