Eribulin Mesylate as Second-Line Therapy for Locally Advanced, Unresectable, or Metastatic Pancreatic Cancer Patients

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