Electroporation Potentiated Immunotherapy in Cancer (EPIC-1)

Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery

Status and phase: Active, not recruiting; Phase 2

Conditions: Pancreas Cancer, Metastatic

Treatments: Drug: Pembrolizumab; Device: Irreversible electroporation

Study type: Interventional

Funder types: Other

Identifiers

NCT04835402

N-20200085 (Other Identifier)

2020-004536-22 (EudraCT Number)

EPIC-1

Details and patient eligibility

About

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

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Intervention

Experimental group

Description:

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

Treatment:

Device: Irreversible electroporation

Drug: Pembrolizumab