Anti-Tumor Immunity Induced by IRE of Unresectable Pancreatic Cancer

IRE: Anti-Tumor Immunity Induced by IRE of Unresectable Pancreatic Cancer

This protocol will study the impact of Irreversible electroporation (IRE) on immune response in patients diagnosed with unresectable pancreatic cancers smaller than 5.0 cm. It will profile the immune response to IRE of unresectable pancreatic cancers. The intra-tumoral and systemic immune response to IRE will be determined and compared to pre-ablated pancreatic cancer specimens and historical control specimens.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Device: NanoKnife LEDC System

Detailed Description

Thirty patients with histologically confirmed locally advanced pancreatic adenocarcinoma (≤5.0cm) will undergo percutaneous irreversible electroporation of the tumor using CT and ultrasound guidance. Blood will be drawn for research before IRE. Blood and tissue samples will be used.

After IRE, patients will be carefully monitored and systemic immune responses are registered. Follow-up will consist of frequent CT and MRI scanning, as well as serum CA19.9 tumor marker and quality of life questionnaires and overall survival (OS).

The investigators hypothesize that IRE in the pancreas will induce good symptom palliation without causing severe complications as well as perfect systemic immune response.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510665
      • Fuda Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Radiologic confirmation of unresectable pancreatic cancer by at least CT of chest and abdomen
• Screening must be performed no longer than 2 weeks prior to study inclusion
• 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;
• Successful down staging after (radio)chemotherapy from previous unresectable/borderline tumor to resectable tumor;
• 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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; The patients without treatment
Experimental: NanoKnife LEDC System; 90 pulses of 70 microseconds each in duration will be administered per electrode pair.	Device: NanoKnife LEDC System; Irreversible electroporation (IRE) is a new, minimal-invasive image-guided treatment method for tumors not amenable for surgical resection or thermal ablation, due to vicinity near vital structures such as vessels and bile ducts. With IRE, multiple electrical pulses are applied to tumorous tissue. These pulses alter the existing transmembrane potential of the cell membranes, and create 'nanopores', after which the cell dies through loss of homeostasis.; Other Names: NanoKnife

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the intra-tumoral and systemic immune response to IRE in unresectable pancreatic cancers	Determine number (percentage via flow cytometry), phenotype and functionality of tumor infiltrating lymphocytes in ablated pancreatic cancer; Determine morphology and histology of regional lymph node after IRE; Quantify T cell response (IUs of IL2 and IFN gamma, and T cell specific cells as measured by number of spots on an elispot assay) to tumor associated antigens using in vitro assays of T cell proliferation and function (cytokine release, elispot, peptide-MHC)	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison immune response between non-ablated and ablated pancreatic cancer and pre-ablated and post ablated serum	Compare serum cytokine and chemokine expression (in IU) between patients undergoing or not undergoing tumor ablation; Characterize cytokine and chemokine expression (in IU) in ablated tissue and in pre-ablated and post-ablated serum over time; Compare intra-tumoral lymphocyte populations (percentage via flow cytometry) in ablated tumor tissue with paraffin embedded specimens for tumors that are matched for age, tumor size and histology.	24 Months

Other Outcome Measures

Outcome Measure	Time Frame
Overall survival and (local and distant) progression-free survival.	60 Months

Collaborators and Investigators

• Sponsor: Fuda Cancer Hospital, Guangzhou
• Investigators: Study Chair: Lizhi l Niu, M.D.,PHD., Fuda Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: January 16, 2015
• First Posted (Estimate): January 22, 2015

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: February 1, 2019

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: JF-20150113(4)