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First patient for trial with promising repurposed drug in pancreatic cancer

First patient for trial with promising repurposed drug in pancreatic cancer


Brussels – The first patient for ORIENTATE was enrolled in Verona, Italy. The clinical trial will explore the repurposing of decitabine against advanced, refractory, KRAS-dependent pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer. 

The ORIENTATE-trial is a proof-of-concept, biomarker-driven, phase-II trial for patients with PDAC, a very aggressive and often deadly type of cancer. Most patients with PDAC have an advanced metastatic disease at the time of diagnosis. In addition to the options for treatments being limited and highly toxic, the outcome is also very poor since many pancreatic tumours are refractory to therapy.

The ORIENTATE-trial, or tailOred dRug repurposIng of dEcitabine in KRAS-dependeNt refracTory pAncreaTic cancEr-trial, will investigate the impact of decitabine - a drug approved by the American Food & Drug Administration (FDA) for the treatment of myelodysplasia and acute myeloid leukaemia (AML)- on patients with advanced, refractory KRAS-dependent PDAC.

In almost all PDACs, KRAS gene mutations are present that stimulate the pancreatic cells to grow in an uncontrolled manner, fostering tumour development and progression. A proportion of advanced tumours remains reliant on this KRAS pathway to grow, and pre-clinical research already showed that these tumours specifically respond to decitabine. This offers a promising treatment strategy.

The trial has a two-stage design. At first, 9 patients will be recruited. If no response to the treatment is observed, the trial will be stopped for futility. In case of 1 or more responses, another 8 patients will be enrolled. The first patient in the first stage of the trial was enrolled this week in Verona, Italy.  

This is a very innovative approach to the treatment of pancreatic cancer. No drugs exist to target the mutations that activate KRAS in pancreatic cancer so here, decitabine will do this indirectly. Moreover, the researchers will first identify those tumours that harbour this specific vulnerability, using a personalised approach based on transcriptomic profiling, says Professor Ilse Rooman, director of the pancreatic programme at the Anticancer Fund.

Why we believe in this trial

The clinical study is an initiative from the Regina Elena National Cancer Institute (IRCCS) and the University of Verona, both in Italy. The principal investigators are Luca Cardone from the IRCCS and Michele Milella of the University of Verona. Next to providing scientific and strategic input to the investigators, the Anticancer Fund is also financing the study. The amount allocated to this trial is close to 225.000 euro.

The Anticancer Fund decided to support this trial as it clearly focuses on an unmet need: pancreatic cancer patients have few options for treatment today, and specific research is urgently needed. Moreover, as decitabine is a repurposed drug, the investments required to implement this treatment strategy are low and patients would have easy access to this treatment.

Luca Cardone, Scientific Principal Investigator, adds: There is a tremendous need to boost pancreatic cancer patients' prognosis by efficient and personalised therapies. We are grateful to the Anticancer Fund’s contribution supporting the ORIENTATE trial, the first biomarker-driven, personalised drug repurposing trial in advanced pancreatic cancer patients. We are delighted for the tremendous scientific and strategic support from the Anticancer Fund to make this clinical trial real!.

Michele Milella, Clinical Principal Investigator, agrees: This trial adds another important chance of treatment for advanced PDAC patients and builds on the experience of genomic profiling in advanced PDAC carried out in Verona by the ARC-NET Research Centre in collaboration with the International Cancer Genome Consortium (ICGC). Genomic vulnerabilities identify potential treatments in approximately 25-30% of PDAC patients. Therefore, we hope testing for KRAS-dependency with transcriptomics will add yet another option for these patients, thanks to the effort and support the ACF has put in this trial!.

Additional information

More details about the trial here.

Get to know more about drug repurposing in oncology.

Read the blog Professor Ilse Rooman and Guy Buyens, medical director of the Anticancer Fund, recently wrote about pancreatic cancer and why raising awareness is important.