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.