QT Interval Prolongation Study of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors

Personal history of unexplained syncope within the last year prior to entry

Inclusion Criteria

• Patients with histologically or cytologically confirmed advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
• Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy /= 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
• Patients must have a sinus rhythm and QRS /= 40 mL/min per the Cockcroft and Gault formula.
• Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >/= 1.5 x 10^9/L, hemoglobin >/= 10.0 g/dL (a hemoglobin /= 100 x 10^9/L.
• Adequate liver function as evidenced by bilirubin >/= 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) 30% of bone marrow.
• Have received prior treatment with mitomycin C or nitrosourea.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
• Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (e.g. radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks.
• Patients with meningeal carcinomatosis.
• Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
• Patients with marked baseline prolongation of QT/QTc interval (QTc interval > 500 msec).
• Patients with a history of additional risk factors for Torsades des pointes (e.g., heart failure, cardiac ischemia, recent Myocardial Infarction (MI), family history of Long QT Syndrome).
• Patients with uncontrolled metabolic disorders (e.g hypokalemia, hypercalcemia and hypomagnesemia) at entry to the study.
• Patients treated with antiarrythmic drugs or other medications that prolong the QT/QTc, that cannot be discontinued prior to entry into the study phase.
• Patients with implantable pacemaker or automatic implantable cardioverter defibrillator (AICD).
• .Bradycardia (defined as /= 5 years previously with no subsequent evidence of recurrence.
• Patients with pre-existing neuropathy > Grade 2.
• Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
• Patients who participated in a prior eribulin mesylate clinical trial.
• Patients with pericardial effusion or pericardial metastases.