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Pancreas Cancer, MetastaticPhase 2EPIC-1NCT04835402

Electroporation Potentiated Immunotherapy in Cancer

A Phase 2 study testing Pembrolizumab and Irreversible electroporation in people with Pancreas Cancer, Metastatic, run by Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery at 1 site in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreas Cancer, Metastatic
What is being tested?
Pembrolizumab and Irreversible electroporation
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteDenmark
Study dates
26 May 2021to Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically verified pancreatic adenocarcinoma, based on either a biopsy of the primary tumor or a metastasis
  • One liver metastasis treatable by IRE (as determined by MDT at Aalborg University Hospital)
  • One tumor lesion suited for repeated biopsy by transcutaneous core needle (preferably another lesion than that used for IRE)
  • At least one measurable lesion (RECIST version 1.1) other than the liver metastasis to be treated by IRE
  • At least one course of chemotherapy for metastatic or inoperable disease discontinued due to treatment failure or intolerance
  • Performance status 0-1
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  • ASA ≤ 3
  • ≥ 18 years of age
  • Written and orally informed consent
  • Sufficient available histological tumor material stored in biobank or obtainable by new biopsy
  • Patient acceptance of collection of blood samples for translational research and two additional biopsies during treatment
  • Adequate bone marrow function, liver function, and renal function (within 7 days prior to enrollment):
  • Neutrophils (ANC) ≥ 1.5 x 109/l
  • Platelet count ≥ 100 x 109/l
  • Hemoglobin ≥ 6 mmol/l
  • Plasma bilirubin ≤ 1.5 x ULN
  • Plasma alanine transaminase (ALAT) < 5 x ULN
  • Plasma creatinine ≤ 1.5 x ULN
  • INR ≤ 1.5

Who cannot join

  • Underlying medical disease not adequately treated (e.g. poorly regulated diabetes and symptomatic cardiac disease)
  • Prior or current autoimmune disorder with risk of serious toxicity during treatment with checkpoint inhibitor
  • Acute myocardial infarction, cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within 6 months from start of treatment
  • Previous reception of allogeneic stem cells or solid organ donation
  • Active infection requiring systemic therapy within 7 days prior to treatment initiation
  • Positive HIV, HBV, and HCV test results (prior testing or new testing in patients at risk)
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  • Active psychiatric disease or history of drug or alcohol abuse affecting participation
  • 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
  • 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
  • Coexisting malignant disease, except non-melanoma skin cancer
  • Symptomatic or untreated CNS metastases
  • Liver cirrhosis Child Pugh >A
  • 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
  • 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)
  • Previous immunotherapy
  • Patients referred from a hospital outside of Denmark
  • Major dilation of veins or bowel obstructing the needle path
  • Persistent atrial fibrillation
  • Metal objects (e.g. biliary SEMS) within 5 cm of ablation target
  • Cardiac pacemaker or ICD, that cannot be safely disconnected during IRE treatment

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Department of Oncology

    Aalborg, North Denmark, DK-9000

Other trials in Denmark

About this study

Official title: A Phase II Study of Electroporation Potentiated Immunotherapy in Liver Metastatic

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

Read the detailed description

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.

Being tested
Pembrolizumab, Irreversible electroporation
Keywords
Irreversible electroporation, Pembrolizumab, Immune checkpoint inhibitor
Medical subject headings
Pancreatic Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Irreversible electroporation (NanoKnife(tm), Angiodynamics)

    400mg every 6 weeks

  • Irreversible electroporationDevice

    Also called NanoKnife(tm) (Angiodynamics)

    Percutaneous ablation of one liver metastasis

Study groups in NCT04835402
Study groupRoleWhat they receive
InterventionExperimentalDay 1: Pembrolizumab 400mg Day 10: Irreversible electroporation Day 42/84/126/168: Pembrolizumab 400mg
Receives: Drug: Pembrolizumab; Device: Irreversible electroporation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate (ORR) according to RECIST 1.1

    (in patients receiving at least one dose of pembrolizumab, IRE and an evaluable CT-scan)

    Measured: 6 months after treatment start

  2. Serious adverse reaction (SAR) rate according to CTCAE v5

    (in patients receiving at least one dose of pembrolizumab)

    Measured: cumulative after 12 months after treatment start

Secondary outcomes (24)

  1. Median overall survival

    Measured: Through study completion, an average of 1 year

  2. Median progression-free survival

    Measured: Through study completion, an average of 1 year

  3. ORR

    (in patients that have received at least one dose of pembrolizumab and an evaluable CT-scan)

    Measured: 2 months, 4 months and 6 months after treatment start

  4. 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)

    Measured: 8 weeks after treatment start

  5. 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)

    Measured: 2 months, 4 months and 6 months after treatment start

  6. Survival rate

    Measured: 6 months and 12 months after treatment start

  7. Progression-free survival rate

    Measured: 6 months and 12 months after treatment start

  8. 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)

    Measured: 2 months, 4 months, 6 months, 8 months, 10 months and 12 months after treatment start

  9. 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)

    Measured: 2 months, 4 months, 6 months, 8 months, 10 months and 12 months after treatment start

  10. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  11. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  12. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  13. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  14. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  15. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  16. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  17. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  18. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  19. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  20. 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)

    Measured: 8 days, 11 days, 52 days after treatment start

  21. Histological tumor regression grade in tumor biopsies after pembrolizumab and after pembrolizumab + IRE compared to baseline

    (based on the CAP regression grading system)

    Measured: 10 days and 52 days after treatment start

  22. 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)

    Measured: 10 days and 52 days after treatment start

  23. 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)

    Measured: 10 days and 52 days after treatment start

  24. Adverse event rate (CTCAEv5, all grades)

    (all events registered during active treatment and follow-up)

    Measured: cumulative after 12 months after treatment start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start26 May 2021
  3. Primary completion7 Mar 2022
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04835402
Sponsor's protocol ID
EPIC-1
Other IDs
2020-004536-22, N-20200085
Acronym
EPIC-1
Status last verified
Mar 2022
First submitted
24 Mar 2021
Last updated
9 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Irreversible electroporation in people with Pancreas Cancer, Metastatic, run by Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) according to RECIST 1.1 (time frame: 6 months after treatment start). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04835402.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2022.

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