Electroporation Potentiated Immunotherapy in Cancer

NCT ID: NCT04835402

Last Updated: 2022-03-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-26
• Study Completion Date: 2025-12-31

Brief Summary

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

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.

Conditions

Pancreas Cancer, Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

400mg every 6 weeks

Irreversible electroporation

Intervention Type: DEVICE

Percutaneous ablation of one liver metastasis

Interventions

Pembrolizumab

400mg every 6 weeks

Intervention Type: DRUG

Irreversible electroporation

Percutaneous ablation of one liver metastasis

Intervention Type: DEVICE

Other Intervention Names

Irreversible electroporation (NanoKnife(tm), Angiodynamics); NanoKnife(tm) (Angiodynamics)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

Aalborg University

OTHER

Sponsor Role: collaborator

Danish Cancer Society

OTHER

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

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

Professor of surgery, Consultant surgeon, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Morten Ladekarl, DMSc

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology

Locations

Department of Oncology

Aalborg, North Denmark, Denmark

Countries

Denmark

Other Identifiers

2020-004536-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

N-20200085

Identifier Type: OTHER

Identifier Source: secondary_id

EPIC-1

Identifier Type: -

Identifier Source: org_study_id