Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma
Condition: Recurrent Osteosarcoma
MeSH terms: Osteosarcoma; Recurrence
Intervention: Eribulin Mesylate; Pharmacological Study
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Halichondrin B
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 12 Years
Maximum age: 49 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well eribulin mesylate works in treating patients with
      osteosarcoma that has come back after treatment (recurrent) or has not responded to treatment
      (refractory). Microtubule inhibitors, such as eribulin mesylate, may stop or slow the growth
      of tumor cells by disrupting the cell cycle.
    

Eligibility criteria:

        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