Title: Treatment of unresectable Locally Advanced Pancreas (LAP) cancer with Percutaneous Irreversible Electroporation (PIE) following initial systemic chemotherapy : a feasibility randomised controlled trial (The LAP-PIE) trial.
Funder: Department of Health and Social Care

Abstract: 1. Research question Is IRE therapy beneficial to patients with locally advanced and unresectable pancreas cancer? 2. Background Surgery (pancreatic resection) is the only treatment with the potential to cure pancreatic cancer. However only 10 to 20% of people are eligible for surgery. One of the major reasons is that the cancer has spread into the surrounding structures, often the superior mesenteric vein and/or artery. This circumstance affecting about 30% of all patients is termed locally advanced pancreatic cancer (LAPC). Currently, the recommended treatment for LAPC is chemotherapy. Those with a response to chemotherapy would again be considered for resection. Overall 65% of patients post chemotherapy remain with localised but unresectable disease (UK SCALOP trial induction protocol data). These individuals will be invited to participate in this study. Irreversible electroporation (IRE) is a new method of treating localised cancers which are not suitable for surgery. The IRE treatment destroys cancer cells using electricity. Under general anaesthetic the IRE electrodes are inserted into the borders of the pancreas cancer prior to an electrical charge being passed through the cancer. Early studies of IRE in pancreas cancer show that IRE treatment may increase how long people with LAPC live (median survival 25months) but these studies were not controlled or randomised. The improved outcome could therefore be related to patient selection. In addition major complications may result from this treatment (eg acute pancreas inflammation, acute pancreatitis), particularly when the treatment is carried out at open surgery rather than percutaneously. There is therefore uncertainty on the clinical application of pancreas IRE therapy. 3. Aims and objectives The aim of this study is to assess the feasibility of performing IRE therapy in patients with locally advanced pancreas cancer (LAPC) whose disease remains locally unresectable following initial chemotherapy. 4. Methods We are proposing to run a small-scale study (a &ldquo;feasibility study&rdquo;) that will recruit 50 people with LAPC whose disease has remained localised to the pancreas but is unresectable following initial chemotherapy. All will be offered further chemotherapy according to standard centre protocols and half will also be offered IRE. We will assess whether patients are willing to participate in this study and complete the designated treatment. We will assess the completeness of pancreas IRE therapy (technical success) and the complications of the procedure. We will follow the study participants for 12 months assessing their quality of life and cancer response from imaging. 5. Timelines for delivery 36 months. 6 months setup, 15 months recruitment, 12 months follow up and 3 months data cleaning, analysis and preparation of subsequent trial application. 6. Anticipated impact and dissemination This is the first randomised trial of IRE therapy for locally advanced pancreas cancer and will have implications for all patients presenting with pancreas cancer and healthcare providers. Outcomes will be disseminated through healthcare meetings, specialist societies, pancreas charities, patient groups and social media. The main purpose of this study is to collect information allowing the design a larger study addressing whether IRE is beneficial and provides value for money.

Lay abstract: 1. Aim of the research We wish to improve the length and quality of life of people with pancreas cancer. 2. Background Surgery (pancreatic resection) is the only treatment with the potential to cure pancreatic cancer. Only 10 to 20 out of every 100 people are eligible for surgery. One of the major reasons is that the cancer has spread into the surrounding structures (locally advanced pancreatic cancer (LAPC)). Currently, the recommended treatment for LAPC is chemotherapy (drugs which destroy cancer). Those in whom the chemotherapy prevents growth or spread of the cancer have an improved survival. They are re-assessed for surgery but the cancer usually remains unresectable. Irreversible electroporation (IRE) is a new method of treating cancer. The IRE treatment destroys cancer cells by electricity. Under general anaesthetic the IRE probes are inserted into the pancreas cancer prior to an electrical charge being passed through the cancer. Early studies in pancreas cancer suggest that IRE treatment may increase how long people with LAPC live. However major complications may result from this treatment (eg acute pancreas inflammation, acute pancreatitis) resulting in uncertainty on its use. 3. Design of the study We are proposing to run a small-scale study (a &ldquo;feasibility study&rdquo;) that will recruit 50 people with LAPC whose disease has remained localised to the pancreas but is unresectable following initial chemotherapy. All will be offered further chemotherapy according to standard centre protocols and half will also be offered IRE. We will assess whether patients are willing to participate in this study. We will follow the study participants for 12 months assessing length and quality of life and cancer response from imaging. The main purpose of this study is to collect information which will be used to design a larger study to determine whether IRE is beneficial and whether it provides value for money. 4. Patient and public involvement These proposals have been reviewed and supported by the Pancreas Cancer UK patient Network. The Director of Operations for pancreas UK and a patient representative have been involved in the design and presentation of this study. They will be actively involved in the trial management group. 5. Dissemination of results This is the first detailed study of this new treatment for pancreas cancer and will be important to all patients presenting with pancreas cancer and those providing and funding healthcare. Outcomes will be disseminated through healthcare meetings, specialist societies, pancreas charities, patient groups and by social media. The trial PPI representatives will assist with the review and dissemination of all information on the trial outcomes. _x0016_

Research activity codes: 6.1 PHARMACEUTICALS;6.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS