Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial
Introduction Pancreatic cancer is the fourth-leading cause of cancer-related death in developed countries. Despite advances in systemic chemotherapy, the mainstay of curative therapy for non-metastatic disease is surgical resection. However, the perioperative period is characterised by stress and in...
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BMJ Publishing Group
2020-09-01
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| Series: | BMJ Open |
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| author | Phillip Knebel Thilo Hackert Markus W Büchler Ilse Rooman Markus K Diener Felix J Hüttner André L Mihaljevic Oliver Strobel Gauthier Bouche Johannes Hüsing |
| author_facet | Phillip Knebel Thilo Hackert Markus W Büchler Ilse Rooman Markus K Diener Felix J Hüttner André L Mihaljevic Oliver Strobel Gauthier Bouche Johannes Hüsing |
| author_sort | Phillip Knebel |
| collection | DOAJ |
| description | Introduction Pancreatic cancer is the fourth-leading cause of cancer-related death in developed countries. Despite advances in systemic chemotherapy, the mainstay of curative therapy for non-metastatic disease is surgical resection. However, the perioperative period is characterised by stress and inflammatory reactions that can contribute to metastatic spread and disease recurrence. Catecholamines and prostaglandins play a crucial role in these reactions. Therefore, a drug repurposing of betablockers and cyclooxygenase inhibitors seems reasonable to attenuate tumour-associated inflammation by inhibiting psychological, surgical and inflammatory stress responses. This may cause a relevant antitumourigenic and antimetastatic effect during the perioperative period, a window for cancer-directed therapy that is currently largely unexploited.Methods and analysis This is a prospective, single-centre, two-arm randomised, patient and observer blinded, placebo-controlled, phase-II trial evaluating safety and feasibility of combined perioperative treatment with propranolol and etodolac in adult patients with non-metastatic cancer of the pancreatic head undergoing elective pancreatoduodenectomy. 100 patients fulfilling the eligibility criteria will be randomised to perioperative treatment for 25 days perioperatively with a combination of propranolol and etodolac or placebo. Primary outcome of interest will be safety in terms of serious adverse events and reactions within 3 months. Furthermore, adherence to trial medication will be assessed as feasibility outcomes. Preliminary efficacy data will be evaluated for the purpose of power calculation for a potential subsequent phase-III trial. The clinical trial is accompanied by a translational study investigating the mechanisms of action of the combined therapy on a molecular basis.Ethics and dissemination The PROSPER-trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042875) and the Ethics Committee of the Medical Faculty of the University of Heidelberg (reference number AFmo-385/2018). The final trial results will be published in a peer-reviewed journal and will be presented at appropriate national and international conferences.Trial registration numbers DRKS00014054; EudraCT number: 2018-000415-25. |
| format | Article |
| id | doaj-art-9575ce61f51c4f65b38ffec971b9d983 |
| institution | Kabale University |
| issn | 2044-6055 |
| language | English |
| publishDate | 2020-09-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-9575ce61f51c4f65b38ffec971b9d9832025-01-09T05:45:12ZengBMJ Publishing GroupBMJ Open2044-60552020-09-0110910.1136/bmjopen-2020-040406Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trialPhillip Knebel0Thilo Hackert1Markus W Büchler2Ilse Rooman3Markus K Diener4Felix J Hüttner5André L Mihaljevic6Oliver Strobel7Gauthier Bouche8Johannes Hüsing9Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany6 Department of Surgery, Heidelberg University Hospital, Heidelberg, GermanyLaboratory of Medical and Molecular Oncology, Vrije Universiteit Brussel, Brussel, BelgiumThe Study Center of the German Surgical Society (SDGC), University of Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyDepartment of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, GermanyDepartment of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany1 Anticancer Fund, Meise, BelgiumCoordination Center for Clinical Trials, Heidelberg University, Heidelberg, GermanyIntroduction Pancreatic cancer is the fourth-leading cause of cancer-related death in developed countries. Despite advances in systemic chemotherapy, the mainstay of curative therapy for non-metastatic disease is surgical resection. However, the perioperative period is characterised by stress and inflammatory reactions that can contribute to metastatic spread and disease recurrence. Catecholamines and prostaglandins play a crucial role in these reactions. Therefore, a drug repurposing of betablockers and cyclooxygenase inhibitors seems reasonable to attenuate tumour-associated inflammation by inhibiting psychological, surgical and inflammatory stress responses. This may cause a relevant antitumourigenic and antimetastatic effect during the perioperative period, a window for cancer-directed therapy that is currently largely unexploited.Methods and analysis This is a prospective, single-centre, two-arm randomised, patient and observer blinded, placebo-controlled, phase-II trial evaluating safety and feasibility of combined perioperative treatment with propranolol and etodolac in adult patients with non-metastatic cancer of the pancreatic head undergoing elective pancreatoduodenectomy. 100 patients fulfilling the eligibility criteria will be randomised to perioperative treatment for 25 days perioperatively with a combination of propranolol and etodolac or placebo. Primary outcome of interest will be safety in terms of serious adverse events and reactions within 3 months. Furthermore, adherence to trial medication will be assessed as feasibility outcomes. Preliminary efficacy data will be evaluated for the purpose of power calculation for a potential subsequent phase-III trial. The clinical trial is accompanied by a translational study investigating the mechanisms of action of the combined therapy on a molecular basis.Ethics and dissemination The PROSPER-trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4042875) and the Ethics Committee of the Medical Faculty of the University of Heidelberg (reference number AFmo-385/2018). The final trial results will be published in a peer-reviewed journal and will be presented at appropriate national and international conferences.Trial registration numbers DRKS00014054; EudraCT number: 2018-000415-25.https://bmjopen.bmj.com/content/10/9/e040406.full |
| spellingShingle | Phillip Knebel Thilo Hackert Markus W Büchler Ilse Rooman Markus K Diener Felix J Hüttner André L Mihaljevic Oliver Strobel Gauthier Bouche Johannes Hüsing Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial BMJ Open |
| title | Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial |
| title_full | Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial |
| title_fullStr | Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial |
| title_full_unstemmed | Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial |
| title_short | Pancreatic resection with perioperative drug repurposing of propranolol and etodolac: trial protocol of the phase-II randomised placebo controlled PROSPER trial |
| title_sort | pancreatic resection with perioperative drug repurposing of propranolol and etodolac trial protocol of the phase ii randomised placebo controlled prosper trial |
| url | https://bmjopen.bmj.com/content/10/9/e040406.full |
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