PANFIRE Study: Irreversible Electroporation (IRE) to Treat Locally Advanced Pancreatic Carcinoma

Inclusion Criteria:

Screening must be performed no longer than 2 weeks prior to study inclusion.

* Radiologic confirmation of LAPC by at least ceCT of chest and abdomen (with the upper abdomen scanned according to a dedicated 3mm slice multiphase pancreatic tumor protocol), performed maximum 2 weeks prior to the procedure;
* Maximum tumor diameter ≤ 5 cm;
* Histological or cytological confirmation of pancreatic adenocarcinoma;
* Age ≥ 18 years;
* ASA-classification 0 - 3
* Life expectancy of at least 12 weeks;
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion;

  * Hemoglobin ≥ 5.6 mmol/L;
  * Absolute neutrophil count (ANC) ≥ 1,500/mm3;
  * Platelet count ≥ 100\*109/l;
  * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN);
  * ALT and AST ≤ 2.5 x ULN;
  * Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 50 ml/min;
  * Prothrombin time or INR \< 1.5 x ULN;
  * Activated partial thromboplastin time \< 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician);
* Written informed consent;

Exclusion Criteria:

* Resectable pancreatic adenocarcinoma as discussed by our multidisciplinary hepatobiliary team;
* Extrapancreatic metastases;
* Successful down staging after (radio)chemotherapy from previous unresectable/borderline tumor to resectable tumor;
* Stage IV pancreatic carcinoma;
* History of epilepsy;
* History of cardiac disease:

  * Congestive heart failure \>NYHA class 2;
  * Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
  * Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted);
* Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
* Compromised liver function (e.g. signs of portal hypertension, INR \> 1,5 without use of anticoagulants, ascites);
* Uncontrolled infections (\> grade 2 NCI-CTC version 3.0);
* Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment;
* Immunotherapy ≤ 6 weeks prior to the procedure;
* Chemotherapy ≤ 6 weeks prior to the procedure;
* Radiotherapy ≤ 6 weeks prior to the procedure;
* Concomitant use of anti-convulsive and anti-arrhythmic drugs (other than beta blockers used for antihypertensive);
* Allergy to contrast media;
* Any implanted stimulation device;
* Any implanted metal stent/device within the area of ablation that cannot be removed;
* Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study;

Of note, patients with contra-indications for MRI will not be excluded from participation: in this case radiologic follow-up will consist of CT-scanning according to protocol.