Immune Response After Pancreatic Cancer Treatment (IRE Immuno)

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?

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Procedure: irreversible electroporation (IRE)

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland
    • Inselhospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing an established procedure for pancreatic cancer. The assignment into either group will be independent of this research proposal and rely completely on clinical judgment. Main outcomes will be changes in immunological short-term and long-term outcomes.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
10 IRE locally advanced; patients undergoing in situ IRE for locally advanced pancreatic	Procedure: irreversible electroporation (IRE); 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.
10 IRE borderline resection; patients undergoing margin accentuation IRE for borderline resectable disease	Procedure: irreversible electroporation (IRE); 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.
10 resection only; patients undergoing surgical resection only

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Mathias Worni, MD, Inselspital Berne

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Actual): February 25, 2020
• Study Completion (Actual): February 25, 2020

Study Registration Dates

• First Submitted: December 20, 2016
• First Submitted That Met QC Criteria: March 2, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2016-02037