$0.00
Shopping Cart
Facebook-f Instagram
DONATE
Donate

Clinical Trial Record

Return to Clinical Trials

Electroporation Potentiated Immunotherapy in Cancer

2021-05-26

2022-03-07

2025-12

8

Study Overview

Electroporation Potentiated Immunotherapy in Cancer

The study is investigating the efficacy and safety of combined irreversible electroporation (IRE) and checkpoint inhibition in metastatic pancreatic cancer.

The aim of the study is to investigate whether checkpoint inhibition in conjunction with IRE of a single liver metastasis can elicit a systemic anticancer immune response in patients with pancreatic cancer. Adult patients, in WHO performance status 0-1, with liver metastatic pancreatic cancer, intolerant to or progressing on first or further lines of chemotherapy can enter the trial. Pembrolizumab infusion is given every six weeks for up to six months. IRE of a single liver metastasis is performed between the first and second pembrolizumab infusion. Response to the therapy is examined by CT (RECIST) on non-IRE-ablated lesions every 2 months. Assessments of changes in peripheral blood immune cell composition, tumor gene expression and tumor infiltrating lymphocytes is performed on serial biopsies and blood samples.

  • Pancreas Cancer, Metastatic
  • DRUG: Pembrolizumab
  • DEVICE: Irreversible electroporation
  • EPIC-1
  • 2020-004536-22 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )
  • N-20200085 (OTHER Identifier) (OTHER: The North Denmark Region Committee on Health Research Ethics)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2021-03-24  

N/A  

2022-03-08  

2021-04-06  

N/A  

2022-03-09  

2021-04-08  

N/A  

2022-03  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Intervention

Day 1: Pembrolizumab 400mg Day 10: Irreversible electroporation Day 42/84/126/168: Pembrolizumab 400mg

DRUG: Pembrolizumab

  • 400mg every 6 weeks

DEVICE: Irreversible electroporation

  • Percutaneous ablation of one liver metastasis
Primary Outcome MeasuresMeasure DescriptionTime Frame
Objective response rate (ORR) according to RECIST 1.1(in patients receiving at least one dose of pembrolizumab, IRE and an evaluable CT-scan)6 months after treatment start
Serious adverse reaction (SAR) rate according to CTCAE v5(in patients receiving at least one dose of pembrolizumab)cumulative after 12 months after treatment start
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Median overall survivalThrough study completion, an average of 1 year
Median progression-free survivalThrough study completion, an average of 1 year
ORR(in patients that have received at least one dose of pembrolizumab and an evaluable CT-scan)2 months, 4 months and 6 months after treatment start
Clinical benefit ratio(defined as objective response or stable disease for at least 8 weeks during treatment in patients receiving at least one dose of pembrolizumab, IRE and an evaluable CT-scan)8 weeks after treatment start
Serum CA-19-9 response(response defined as a decrease of at least 20 % observed during treatment in patients with elevated CA 19-9 at baseline)2 months, 4 months and 6 months after treatment start
Survival rate6 months and 12 months after treatment start
Progression-free survival rate6 months and 12 months after treatment start
Mean difference in perceived quality of life measured by EORTC QLQ-C30 v3(for subscales: Global health status, Physical functioning, Fatigue, Nausea and vomiting, Pain, Appetite loss and Diarrhea)2 months, 4 months, 6 months, 8 months, 10 months and 12 months after treatment start
Mean difference in nutrition status measured by PG-SGA-SF(difference in total numerical score of the patient-generated subjective global assessment (short form) PG-SGA(c) SF (range 0-37, lower is better)2 months, 4 months, 6 months, 8 months, 10 months and 12 months after treatment start
Difference in peripheral blood naïve T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood effector memory T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood central memory T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood effector T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood terminally differentiated effector T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood exhausted T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood regulatory T cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood conventional dendritic cell type 1 count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood conventional dendritic cell type 2 count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood plasmacytoid dendritic cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Difference in peripheral blood myeloid-derived suppressor cell count prior to IRE-treatment, 1 day after IRE-treatment and 6 weeks after IRE-treatment compared to baseline(based on flow cytometry measures of naïve, EM, CM, EFF, TE, EX T cells, Tregs, cDC1, cDC2, pDC and MDSC concentrations)8 days, 11 days, 52 days after treatment start
Histological tumor regression grade in tumor biopsies after pembrolizumab and after pembrolizumab + IRE compared to baseline(based on the CAP regression grading system)10 days and 52 days after treatment start
Difference in tumor RNA expression after pembrolizumab and after pembrolizumab + IRE compared to baseline(based on NanoString RNA panCancer IO 360 gene panel. Analysis will explore the cancer-immunological mechanisms of the therapy in order to guide future studies. No specific outcomes are predetermined)10 days and 52 days after treatment start
Difference in (histological) tumor infiltrating leukocyte (TIL) pattern after pembrolizumab and after pembrolizumab + IRE compared to baseline(Based on analysis by immunohistochemistry. The relative concentration of leukocytes will be estimated and compared. The exact subpopulations of leukocytes will be based on the findings in outcomes 12 and 14, to validate the results)10 days and 52 days after treatment start
Adverse event rate (CTCAEv5, all grades)(all events registered during active treatment and follow-up)cumulative after 12 months after treatment start

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    Inclusion Criteria:
    1. Histologically verified pancreatic adenocarcinoma, based on either a biopsy of the primary tumor or a metastasis 2. One liver metastasis treatable by IRE (as determined by MDT at Aalborg University Hospital) 3. One tumor lesion suited for repeated biopsy by transcutaneous core needle (preferably another lesion than that used for IRE) 4. At least one measurable lesion (RECIST version 1.1) other than the liver metastasis to be treated by IRE 5. At least one course of chemotherapy for metastatic or inoperable disease discontinued due to treatment failure or intolerance 6. Performance status 0-1 7. ASA ≤ 3 8. ≥ 18 years of age 9. Written and orally informed consent 10. Sufficient available histological tumor material stored in biobank or obtainable by new biopsy 11. Patient acceptance of collection of blood samples for translational research and two additional biopsies during treatment 12. Adequate bone marrow function, liver function, and renal function (within 7 days prior to enrollment):
    1. Neutrophils (ANC) ≥ 1.5 x 109/l 2. Platelet count ≥ 100 x 109/l 3. Hemoglobin ≥ 6 mmol/l 4. Plasma bilirubin ≤ 1.5 x ULN 5. Plasma alanine transaminase (ALAT) < 5 x ULN 6. Plasma creatinine ≤ 1.5 x ULN 7. INR ≤ 1.5
    Exclusion Criteria:
    1. Underlying medical disease not adequately treated (e.g. poorly regulated diabetes and symptomatic cardiac disease) 2. Prior or current autoimmune disorder with risk of serious toxicity during treatment with checkpoint inhibitor 3. Acute myocardial infarction, cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within 6 months from start of treatment 4. Previous reception of allogeneic stem cells or solid organ donation 5. Active infection requiring systemic therapy within 7 days prior to treatment initiation 6. Positive HIV, HBV, and HCV test results (prior testing or new testing in patients at risk) 7. Active psychiatric disease or history of drug or alcohol abuse affecting participation 8. Allergy to active substance or any of the auxiliary agents, including known severe allergy to anesthetic agent, paralytic agent or any of the equipment used during treatment 9. Expected need for systemic corticosteroid or other systemic immunosuppressive drug during the course of this clinical trial. A low dose of e.g. prednisone ≤ 10 mg/day is permitted for maximally 7 consecutive days 10. Coexisting malignant disease, except non-melanoma skin cancer 11. Symptomatic or untreated CNS metastases 12. Liver cirrhosis Child Pugh >A 13. Pregnant or breast-feeding patients. For women of childbearing potential, a negative pregnancy test (minimum sensitivity 25mIU(hCG)/ml) is mandatory prior to inclusion and every month during the trial 14. Women of childbearing potential not willing to use effective methods of contraception during treatment and for 6 months after the end of treatment. Male patients with a fertile partner are also required to secure effective methods of contraception (definition available in protocol) 15. Previous immunotherapy 16. Patients referred from a hospital outside of Denmark 17. Major dilation of veins or bowel obstructing the needle path 18. Persistent atrial fibrillation 19. Metal objects (e.g. biliary SEMS) within 5 cm of ablation target 20. Cardiac pacemaker or ICD, that cannot be safely disconnected during IRE treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

  • Odense University Hospital
  • Aalborg University
  • Danish Cancer Society
  • PRINCIPAL_INVESTIGATOR: Morten Ladekarl, DMSc, Department of Oncology

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

NPCF Pop up

Make-A-Will Month

Snag 6508be92
Learn More
Donate Now Online
Other Ways to Donate