Metastatic pancreatic cancer MedDRA version: 21.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Keytruda
Pharmaceutical Form: Concentrate for suspension for injection
INN or Proposed INN: Pembrolizumab
Current Sponsor code: EPIC2020
Concentration unit: mg/ml milligram(s)/millilitre
C
Sponsors
Ole Thorlacius-Ussing
Eligibility
Sex/Gender
All
Inclusion 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): 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) =65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 - To evaluate the effects of the combined treatment on perceived quality of life and nutritional status - 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) 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 3. Median overall survival (mOS) 4. Median progression-free survival (mPFS) 5. ORR (in patients that have received at least one dose of pembrolizumab and an evaluable CT-scan) 6. 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) 7. 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) 8. Survival rate after 6 and 12 months 9. Progression-free survival rate after 6 and 12 months 10. Mean difference (multiple timepoints) in perceived quality of life (for subscales of EORTC QLQ C-30 v3 including Global health status / QoL (QL2), Physical functioning (PF2), Fatigue (FA), Nausea and vomiting (NV), Pain (PA), Appetite loss (AP) and Diarrhea (DI) 11. Mean difference (multiple timepoints) in nutrition status (numerical score of PG-SGA-SF) 12. Difference in peripheral blood immune cell composition during active treatment and follow-up compared to baseline 13. Histological tumor regression grade in tumor biopsies after pembrolizumab and after pembrolizumab + IRE compared to baseline 14. Difference in tumor RNA expression pattern after pembrolizumab and after pembrolizumab + IRE compared to baseline 15. Mean difference in peripheral blood concentration of cancer immunology associated cytokines during active treatment and follow-up compared to baseline 16. Difference in (histological) leukocyte infiltration pattern after pembrolizumab and after pembrolizumab + IRE compared to baseline 17. Difference in detectable peripheral blood cell-free DNA mutations and amount after pembrolizumab and after pembrolizumab + IRE compared to baseline 18. Adverse event rate (CTCAEv5, all grades);Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
Denmark
Contacts
Public ContactClinical trial information
Morten Ladekarl
Outcome results
None listed