PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer

Inclusion Criteria:

• Radiological and histopathologically proven stage IV pancreatic cancer (according tothe AJCC staging system for pancreatic cancer);
• Primary oligometastatic disease, defined as at least 1 hepatic metastasis butoccurrence of other metastases is not necessarily restricted to the liver, maximum ofmetastases is to be determined on a case by case basis by the multidisciplinary tumorboard.
• Primary tumor is in situ.
• A minimum of 4 cycles of FOLFIRINOX chemotherapy is required but with the explicit aimto strive for completion of 8 cycles of FOLFIRINOX before study inclusion, with atleast stable disease on CTscan.
• Age ≥ 18 years.
• World Health Organisation scale (WHO) performance status 0 - 2;
• Adequate bile drainage in case of biliary obstruction.

Exclusion Criteria:

• Trans-mucosal tumor invasion into surrounding duodenum or stomach;
• Active epilepsy (last convulsion < 5 years);
• History of cardiac disease:
• Congestive heart failure > NYHA Class 2
• Active coronary artery disease (defined as myocardial infarction within 6 monthsprior to screening);
• Ventricular cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted; atrial fibrillation isnot contra-indicated);
• Known hypersensitivity to any oligodeoxynucleotides.
• Compromised liver function defined as warning signs of portal hypertension, INR > 1,5without use of anticoagulants, bilirubin > x 1.5 Upper limit of normal range (ULN)ASAT >3.0 x ULN, ALAT >3.0 x ULN.
• Compromised kidney function defined as eGFR <30 ml/min (using the Cockcroft Gaultformula);
• Active autoimmune disease requiring disease-modifying therapy at the time ofscreening: i.e. > 10 mg prednisolone per day or equivalent to this regimen.
• Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time ofscreening on a stable antihypertensive regimen;
• Uncontrolled infections (> grade 2 NCI-CTC version 3.0); requiring antibiotics
• Pregnant or breast-feeding subjects; Women of childbearing potential must have anegative pregnancy test performed within 7 days of the start of treatment;
• Immunotherapy prior to the procedure for the treatment of cancer;
• Previous surgical therapy for pancreatic cancer;
• Second primary malignancy with median 5 year OS < 90%, this excludes adequatelytreated cancers like: non-melanoma skin cancer, in situ carcinoma of the cervix uteri,superficial bladder cancer or other malignancies treated previously without signs ofrecurrence.
• Allergy to contrast agent.
• Allergy to PET tracers 18F-FDG and 18F-BMS-986192 Zr-89-Nivolumab
• Any implanted stimulation device;
• Portal vein or VMS stenosis > 70% (relative contra-indication)
• Any condition that is unstable or that could jeopardize the safety of the subject andtheir compliance in the study.