Eribulin Mesylate in Treating Patients With Recurrent or Refractory Osteosarcoma

A Phase II Study of Eribulin (NSC# 707389) in Recurrent or Refractory Osteosarcoma

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.

PRIMARY OBJECTIVES:

I. To estimate the 4 month progression free survival rate and objective response rate in patients with recurrent osteosarcoma who are administered eribulin (eribulin mesylate) therapy on day 1 and day 8 of 21 day cycles.

SECONDARY OBJECTIVES:

I. To investigate the pharmacokinetics (PK) of eribulin in subjects with recurrent osteosarcoma.

II. To further describe the tolerability of single agent eribulin.

OUTLINE:

Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 5 years.

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