Clinical trial NCT03069599: Immune Response After Pancreatic Cancer Treatment
Official title: 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?
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Pancreatic Cancer
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2017-03-03
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Immunological outcome
timeFrame: 42 days
measure: Immunological outcome
timeFrame: 6 months
measure: Immunological outcome
timeFrame: 9 months
measure: Immunological outcome
timeFrame: 42 days
measure: Immunological outcome
timeFrame: 6 months
measure: Immunological outcome
timeFrame: 9 months
Secondary outcomes:
measure: Number of local tumor recurrences
timeFrame: 42 days
measure: Number of local tumor recurrences
timeFrame: 3 months
measure: Number of local tumor recurrences
timeFrame: 6 months
measure: Number of local tumor recurrences
timeFrame: 9 months
measure: Number of distant tumor recurrences
timeFrame: 42 days
measure: Number of distant tumor recurrences
timeFrame: 3 months
measure: Number of distant tumor recurrences
timeFrame: 6 months
measure: Number of distant tumor recurrences
timeFrame: 9 months
measure: Overall survival
timeFrame: 42 days
measure: Overall survival
timeFrame: 3 months
measure: Overall survival
timeFrame: 6 months
measure: Overall survival
timeFrame: 9 months
measure: Cancer specific survival
timeFrame: 42 days
measure: Cancer specific survival
timeFrame: 3 months
measure: Cancer specific survival
timeFrame: 6 months
measure: Cancer specific survival
timeFrame: 9 months
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselhospital
Study officials:
affiliation: Inselspital Berne
name: Mathias Worni, MD
role: PRINCIPAL_INVESTIGATOR
References: