Electrical stimulation and immunotherapy for pancreatic cancer which has spread to the liver

Phase 1

• Conditions: Metastatic pancreatic cancer; MedDRA version: 21.1Level: LLTClassification code 10033605Term: Pancreatic cancer metastaticSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004536-22-DK
• Lead Sponsor: Ole Thorlacius-Ussing

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-21
• Last Update Posted: 23 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 16

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):
a.Neutrophils (ANC) = 1.5 x 109/l
b.Platelet count = 100 x 109/l
c.Hemoglobin = 6 mmol/l
d.Plasma bilirubin = 1.5 x ULN
e.Plasma alanine transaminase (ALAT) < 5 x ULN
f.Plasma creatinine = 1.5 x ULN
g.INR = 1.5
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

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 at screening is mandatory
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
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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy and safety of combined irreversible electroporation and checkpoint inhibition in liver metastatic pancreatic cancer;Secondary Objective: - To evaluate the effects of the combined treatment on anti-cancer immunity<br>- To evaluate the effects of the combined treatment on perceived quality of life and nutritional status<br>- To evaluate the effects of the combined treatment on tumor biological pathways and gene expression;Primary end point(s): 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)<br>2.Serious adverse reaction (SAR) rate according to CTCAEv5 (in patients receiving at least one dose of pembrolizumab);Timepoint(s) of evaluation of this end point: End of trial