A Dose Finding Study of Eribulin Mesylate and Cetuximab For Patients With Advanced Head and Neck and Colon Cancer

Inclusion Criteria

• Histologically or cytologically confirmed advanced squamous cell cancer of the head and neck with progression after at least one prior therapy. (Chemoradiation is considered one line of therapy)
• In the dose escalation cohorts, patients with advanced colon adenocarcinoma with wild-type kras who have previously received at least two lines of therapy for advanced disease are eligible.
• Life expectancy of at least 3 months
• Patients must be aged 18 years or older
• Patients with measurable tumors according to RECIST .
• Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• No severe concurrent illness that would interfere with protocol therapy.
• Patients must have adequate renal function as evidenced by ≤1.5 mg/dL or creatinine clearance > 40 mL/minute (min).
• Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) > 1.5 x 109/L and platelet count > 100 x 109/L.
• Patients must have adequate hepatic function as evidenced by bilirubin ≤ 1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 3 x ULN (in the case of liver metastases ALT and AST ≤ 5 x ULN).
• Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or below, except for alopecia.
• Patients must be willing and able to comply with the study protocol for the duration of the study.
• Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
• No other active invasive malignancy unless disease free for at least 2 years.

Exclusion Criteria

• In the final expansion cohort, no prior treatment with EGFR inhibitor.
• Patients who received chemotherapy or investigational therapy within 3 weeks before treatment initiation. Radiation must be completed within 2 weeks before treatment initiation.
• Patients with a hypersensitivity to cetuximab.
• Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
• Patients who participated in a prior eribulin mesylate clinical trial, whether or not they received eribulin mesylate.
• Patients with other significant disease or disorders that, in the investigator's opinion, would exclude the patient from the study.
• Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Peri-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• 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.
• Grade 2 or worse neuropathy.
• Significant cardiovascular impairment (history of congestive heart failure > NYHA G II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia.
• QTc > 500 msec