Ensayos clínicos

Inclusion Criteria:

• Patients must have had histologic verification of osteosarcoma at original diagnosis
• Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria, and have relapsed or become refractory to conventional therapy
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
  • Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
  • Bisphosphonates: at least 4 weeks since the completion of therapy with a bisphosphonate
  • Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
• Peripheral absolute neutrophil count (ANC) >= 1000/uL
• Platelet count >= 75,000/uL (transfusion independent)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows: (threshold creatinine values were derived from the Schwartz formula for estimating GFR)
  • Age (12 to < 13 years) - serum creatinine of 1.2 mg/dL
  • Age (13 to < 16 years) - serum creatinine of 1.5 mg/dL (male) and 1.4 mg/dL (female)
  • Age (>= 16 years) - serum creatinine of 1.7 mg/dL (male) and 1.4 mg/dL (female)
• Bilirubin (sum of conjugate + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 units per liter (U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
• Serum albumin > 2 g/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with congenital prolonged QT syndrome
• Patients with a baseline QT/corrected QT (QTc) interval >= 501 msec
• Patients who are receiving drugs that prolong the QTc are not eligible
• Patients who have previously received eribulin, halichondrin B, or analogues of halichondrin B
• Patients who have grade >= 2 peripheral neuropathy
• Patients who are receiving other cancer directed therapy at the time of enrollment
• Patients who have had major surgery within 3 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery
• Pregnancy and breast feeding
  • Female patients who are pregnant are ineligible
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation