The purpose of this study is to determine if the full dose of eribulin mesylate can be safely given with the full dose of cetuximab. The activity of the combination of eribulin mesylate and cetuximab on recurrent head and neck cancer and colon cancer will also be assessed.

To determine if eribulin mesylate, up to a maximum dose of 1.4 mg/m2 day 1 and 8 of a 21 day cycle, can be safely combined with full dose cetuximab for patients with advanced head and neck cancer 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). Patients with unknown Head and Neck primaries are also eligible
• 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with wild-type kras who have previously received at least two lines of therapy for advanced disease are eligible- No longer applicable post February 2013 as all patients have been enrolled to the dose escalation phase
• In the expansion phase for patients with advanced colorectal cancer, only patients with mutated kras who have previously received at least two lines of therapy for metastatic disease will be eligible. Pathology report from diagnosis and report documenting KRAS status to be sent to BrUOG. No longer applicable as this phase of the study has been closed as of 5/6/2014 secondary to the lack of efficacy and activity of the single agent.
• 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

• For Head and Neck patients, no progression while receiving an EGFR inhibitor or within 6 months of stopping treatment with an 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 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