Immune Response After Pancreatic Cancer Treatment

Study Overview
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Brief Summary
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The aim of this project is to describe the differential immunologic responses of patients who undergo in situ IRE, margin accentuation IRE with surgical resection of the primary tumor, and surgical resection of the primary tumor only. The primary hypothesis is that IRE induces a long and sustained activation of the cell-mediated immune system, which is distinct from the immune response after surgical resection only. The primary endpoint of this study is the comparison of the CD4+/CD8+ ratio as an indicator of antitumor immunity both longitudinally within a group after the intervention and over time between the three groups. CD4+/CD8+ ratio will be measured preoperatively and at postoperative days 1, 7, 42, and 180. As a secondary outcome, additional measurements will be taken to more specifically characterize the immune response based on peripheral blood samples. Flow cytometry will be used to quantify cell subsets, and ELISA will be used to measure cytokine levels , at the same time-points as for the primary outcome. Each group of patients as described above will consist of 10 consecutive pancreatic cancer patients. Patients aged 18 or older with resectable, borderline resectable, or locally advanced pancreatic cancer will be included. Patients with locally advanced disease will undergo 3 months of preoperative chemotherapy with monitoring to exclude metastatic disease. Main exclusion criteria are cardiac conduction abnormalities and signs of distant metastasis.

Official Title
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Differential Immunologic Signature After Pancreatic Cancer Treatment: Does Irreversible Electroporation Lead to a Prolonged and Potent T-cell Mediated Immune Response Compared to Surgical Resection?

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Procedure: irreversible electroporation (IRE)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Able to undergo general anesthesia (ASA ≤ 4) Performance status ECOG <=2 (Eastern Cooperative Oncology Group) Life expectancy of at least 6 months Resectable, borderline resectable, or locally advanced pancreatic cancer Patients who have locally advanced disease have to show no tumor progression after 3 month of neo-adjuvant chemotherapy+/-XRT before undergoing in situ IRE Exclusion Criteria: Cardiac AV conduction abnormalities, ventricular fibrillation History of epilepsy Recent history of myocardial infarction (2 months) Evidence of distant metastasis (e.g. liver, lung, peritoneum) Informed consent cannot be given by the patient Known hypersensitivity to the IRE electrodes (stainless steel 304L) Women of childbearing potential who are pregnant, breast feeding, or not taking an adequate method of contraception at the time of procedure

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 10 IRE locally advanced<br>patients undergoing in situ IRE for locally advanced pancreatic | Procedure: irreversible electroporation (IRE)<br>* Irreversible electroporation is an emerging, mainly non-thermal ablative modality. It circumvents some downsides of thermal ablation and has the potential for broad application among patients with pancreatic cancer.<br>|
| 10 IRE borderline resection<br>patients undergoing margin accentuation IRE for borderline resectable disease | Procedure: irreversible electroporation (IRE)<br>* Irreversible electroporation is an emerging, mainly non-thermal ablative modality. It circumvents some downsides of thermal ablation and has the potential for broad application among patients with pancreatic cancer.<br>|
| 10 resection only<br>patients undergoing surgical resection only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological outcome | flowcytometry | 42 days | 
| Immunological outcome | Flowcytometry | 6 months | 
| Immunological outcome | Flowcytometry | 9 months | 
| Immunological outcome | ELISA | 42 days | 
| Immunological outcome | ELISA | 6 months | 
| Immunological outcome | ELISA | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of local tumor recurrences | measured via CT | 42 days | 
| Number of local tumor recurrences | measured via CT | 3 months | 
| Number of local tumor recurrences | measured via CT | 6 months | 
| Number of local tumor recurrences | measured via CT | 9 months | 
| Number of distant tumor recurrences | measured via CT | 42 days | 
| Number of distant tumor recurrences | measured via CT | 3 months | 
| Number of distant tumor recurrences | measured via CT | 6 months | 
| Number of distant tumor recurrences | measured via CT | 9 months | 
| Overall survival | survival of patient | 42 days | 
| Overall survival | survival of patient | 3 months | 
| Overall survival | survival of patient | 6 months | 
| Overall survival | survival of patient | 9 months | 
| Cancer specific survival | survival of patient | 42 days | 
| Cancer specific survival | survival of patient | 3 months | 
| Cancer specific survival | survival of patient | 6 months | 
| Cancer specific survival | survival of patient | 9 months |