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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study of the Halichondrin B Analog E7389 as Second Line Therapy for Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas, Pancreatic Cancer, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: eribulin mesylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (eribulin mesylate)<br>Patients receive E7389 IV on days 1 and 8. | Drug: eribulin mesylate<br>* Given IV<br>* Other names: halichrondrin B analog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (Complete and Partial) Evaluated Using RECIST Criteria | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stable Disease Rate, Evaluated Using RECIST Criteria | Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Up to 3 years | 
| Median Survival Time | Estimated using the Kaplan-Meier method. | Up to 3 years | 
| Overall Survival | Estimated using the Kaplan-Meier method. | At 6 months | 
| Overall Survival | Estimated using the Kaplan-Meier method. | At 1 year | 
| Median Time to Disease Progression | Estimated using the Kaplan-Meier method. | Duration of time from start of treatment until the criteria for progression are met, assessed up to 3 years | 
| Time to Progression | Estimated using the Kaplan-Meier method. Median time to progression | At 6 months | 
| Time to Progression | Estimated using the Kaplan-Meier method. | At 1 year | 
| Response Duration |  | From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years | 
| Toxicity | Types of Gr 3 or greater adverse events that are atleast possibly related to study drug | All patients will be evaluable for toxicity from the time of their first treatment with E7389. | 
| Objective Stable Disease Rate | Objective stable disease rate Using RECIST | Upto 3 years |