Approval of pancreatic cancer trial with perioperative use of β-blocker and anti-inflammatory drug
BRUSSELS - A clinical trial designed to fight pancreatic cancer with the re-use of existing drugs got the green light. The German Federal Institute for Drugs and Medical Devices and the Ethics Committee of the Ruprecht-Karls-University Heidelberg Medical Faculty have approved testing a beta-blocker and an anti-inflammatory drug in the period around surgery among pancreatic cancer patients. Eighty patients with pancreatic cancer that are eligible for surgery will soon be recruited for the phase II trial, called PROSPER.
Low survival chances
Pancreatic cancers have a very poor prognosis and rising incidence. Only 15 to 20 percent of pancreatic ductal adenocarcinoma (the most common form of pancreatic cancer) have no sign of metastasis at diagnosis and are deemed operable. For patients with an operable tumour, upfront surgery is the standard of care followed by adjuvant chemotherapy. Nevertheless, the 5-year overall survival of these patients is approximately 20% and almost 50% relapses within the first year after surgery. Clearly, there is a need to reduce the number of relapses which will improve the overall survival of these patients.
New method with PROSPER
PROSPER (Pancreatic Resection with perioperative Off-label Study of Propranolol and Etodolac – a phase II Randomized trial) tests a combination therapy of propranolol and etodolac. In the period around surgery, the trial promises an effective attenuation of psychological, surgical and inflammatory stress responses that facilitate metastasis of the tumour. This approach is interesting because it uses that critical period of surgery as a window for cancer directed therapy that is currently largely unexploited. Moreover, it does not interfere with current practice or future implementation of new adjuvant chemotherapy regimens.
Safety and feasibility
Since it is the first clinical trial to assess the combination therapy of a beta-blocker and an anti-inflammatory drug during the critical period of pancreatic cancer surgery, safety is the main outcome of interest. Secondly, feasibility will be analysed since the two predominant factors (surgery and adjuvant chemotherapy) for curative treatment must not be affected by the combination of drugs. The research team will also analyse the efficacy of this strategy by measuring survival of the patients.
From idea to trial
“We got the idea to start a clinical trial because we discovered scientific publications with promising preclinical laboratory work and a pilot clinical trial in breast cancer”, explains the Anticancer Fund’s Clinical Research Director Gauthier Bouche. “Positive results with mice were reported, the data in breast cancer patients were encouraging and we wanted to continue exploring that hypothesis, this time in patients.”
Fast results, fast solutions
So the Anticancer Fund which is a non-profit research organisation, started looking for a clinical partner who shares the aim to re-use existing drugs while exploring new methods to fight pancreatic cancer. “When early study results of existing drugs show effectiveness, we are convinced that further development of these treatments is a cheap and quick way to get a new treatment option to patients in need”, explains the Anticancer Fund CEO Lydie Meheus. “We want to focus on treatment options that increase survival and quality of life fast.” The fund collected over € 400.000 to fund the entire trial and to create a biobank so that appropriate translational analyses can be performed once the results are known. Interesting fact: 90% of the budget was given to them by an anonymous donor. This project demonstrates that due to philanthropic support development of valuable treatments for patients is feasible independent from pharma industry but complementary to their new drug development activities.
Heidelberg, centre of expertise
Together with Prof. Dr. Ilse Rooman (Vrije Universiteit Brussel) who acts as the fund’s Programme Director Pancreatic cancer, Bouche reached out to the University Hospital of Heidelberg. Shortly after, the trial idea of the Anticancer Fund grew into a concrete and executable trial protocol. PROSPER will be lead by principal investigators Prof. Dr. med. Markus K. Diener, Dr. med. Felix J. Hüttner and PD Dr. med. Phillip Knebel who work in Heidelberg, a centre of expertise for pancreatic cancer in Europe. Results are expected by the end of 2021.