This phase II trial is studying how well E7389 works as second-line therapy in treating patients with locally advanced, unresectable, or metastatic pancreatic cancer. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVE:

I. To determine the objective response (complete and partial) to E7389 in patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma that progressed after prior gemcitabine hydrochloride-based therapy.

SECONDARY OBJECTIVE:

I. To determine the antitumor activity of E7389, in terms of median survival, 1-year survival rate, response or stable disease duration, toxicity, and time to disease progression, in these patients.

OUTLINE: This is an open-label, multicenter study. Patients receive eribulin mesylate IV on days 1 and 8. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed at 4 weeks. Patients with complete response, partial response, or stable disease are followed every 3 months.

Inclusion Criteria:

• Histologically/cytologically confirmed pancreatic carcinoma (locally advanced, unresectable or metastatic)
• measurable disease (at least 1 lesion accurately measured in at least 1 dimension (longest diameter as >20mm with conventional techniques or >10mm with spiral CT scan)
• >=4 weeks from any major surgery
• Up to 1 prior line of gemcitabine based systemic therapy (single agent/combination therapy) for locally advanced/metastatic disease with evidence of disease progression. Prior therapy with inhibitors of angiogenesis and/or the epidermal growth factor receptor permitted. Last chemotherapy dose >=4 weeks prior to randomization.
• May have received prior 5FU (+/- folinic acid)/gemcitabine given concurrently with radiation as a "radiation sensitizer". Last chemotherapy dose >=4 weeks prior to randomization.
• Prior radiation treatment >=4 weeks prior to randomization
• Age >18 years.
• Life expectancy >=3 months
• ECOG< 2(Karnofsky-60%)
• leukocytes>3,000/mcL
• absolute neutrophil count>1,500/mcL
• platelets>100,000/mcL
• total bilirubin < 1.5 UNL
• AST/ALT≤2.5x institutional ULN
• creatinine within institution limits OR creatinine clearance>60mL/min/1.73m2 for patients with creatinine levels above institution limits
• concurrent use of inhibitors/inducers of CYP3A4 are prohibited during the study treatment period
• effects of E7389 on developing human fetus are unknown. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Ability to understand/willingness to sign written informed consent

Exclusion Criteria:

• chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• May not be receiving other investigational agents
• Known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to E7389
• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study
• Pregnant women excluded because E7389 is an antitubulin agent with the potential for teratogenic/abortifacient effects
• HIV-positive patients on combination antiretroviral therapy are ineligible because of potential for p PK interactions with E7389
• Other active malignancies in past 5 years except for cervical carcinoma in situ and non-melanomatous skin cancer