Safety and Efficacy of Irreversible Electroporation for Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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Pancreatic cancer is 5th leading cause of cancer-related death in Korea. It has a dismal prognosis with very low 5-year survival rate, about 5%. Only 10% of pancreatic cancer patients is diagnosed in operable status. So, most of patients could not be treated with curative resection. Locally advanced pancreatic cancer (LAPC) is defined by defined as surgically unresectable due to vascular encasement (e.g. celiac trunk or superior mesenteric artery) by tumor, but have no evidence of distant metastases. In LAPC patients, systemic chemotherapy with/without radiotherapy was used as a standard therapy, but therapeutic response was very poor. Only less than 30% of patients showed treatment response, and median survival of LAPC patient was only 9 months. Thus, more effective treatment modality is needed for LAPC patients. Irreversible electroporation (IRE) is a soft tissue ablation technique using ultra short but strong electrical fields to create permanent and hence lethal nanopores in the cell membrane, to disrupt the cellular homeostasis. IRE does not cause thermally induced necrosis and has tissue selectivity, so adjacent tissue or vascular structures can be preserved. Several clinical trials using IRE were performed to liver, kidney or lung cancer patients. We will operate IRE procedure to LAPC patients who were previously received standard therapy but showed no response, using NanoKnife IRE device. We will investigate treatment response and safety of IRE.

Conditions
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Locally Advanced Pancreatic Cancer

Intervention / Treatment
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* Device: Irreversible electroporation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed pancreatic cancer patients Locally advanced pancreatic cancer patients. Vascular encasement by tumor was noted in radiological evaluation (CT, MRI or PET-CT) Older than 19 years old and younger than 70 years old Previously treated with systemic chemotherapy or chemoradiotherapy due to locally advanced pancreatic cancer. Exclusion Criteria: Patients with life-threatening systemic disease. Metastatic or borderline-resectable pancreatic cancer patients Patients with seizure history Patients with arrythmia or heart failure Recent history of myocardial infarction (within 1 year) Patients who have implantable electronic devices. (e.g. pacemaker, defibrillator) Patients who have metal devices (e.g. metal stent) around tumor. Coagulopathy patients.

Ages Eligible for Study
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Minimum Age: 19 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: IRE<br>The intervention group | Device: Irreversible electroporation<br>* IRE is operated to tumor under laparotomy or CT-guided percutaneous approach. Unipolar (19G) or bipolar (16G) electrode probe is inserted to around tumor. After insertion of probe, short duration (70-90㎲) of electric current (25 45A) is generated by IRE device (NanoKnife IRE device, AngioDynamics, Queens bury, New York). It is possible to obtain a three-dimensional ablation zone using multiple electrode. IRE can cause apoptosis of tumor cells, without adjacent tissue damage.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is calculated from the date of informed consent acquisition until the date of death. | from 1 month to 3 month | 
| Safety (frequency of procedure-related complication and death) | Safety is evaluated by the frequency of procedure-related complication and death. | from 1 month to 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  | within 1 year | 
| Tumor control |  | within 1 year | 
| Pain control |  | within 1 year | 
| Change in CA 19-9 |  | within 1 year |