The PIONEER study: Novel Therapeutics for Pancreatic Cancer Treatment
In line with Glasgow’s cancer research strategy, which aims to explore and develop novel therapeutic strategies for patient benefit, the Glasgow ECMC is leading the way in early phase clinical studies of novel combination therapies.
Professor Jeff Evans, in collaboration with colleagues in Belfast, Leicester and King's Health Partners ECMCs, has recently opened the PIONEER study; a Phase I study of olaparib in combination with chemo-radiation in locally advanced pancreatic cancer, which aims to investigate the effectiveness of a novel combination treatment strategy.
Patients with inoperable ductal adenocarcinoma of the pancreas (PDAC) are typically treated with capecitabine, a radiation – sensitizer, in combination with radiation therapy. However, the median survival of most patients is only approximately 15 months and hence improved treatments are needed.
Poly (ADP-ribose) polymerases (eg PARP-1) are enzymes which play a critical role in signaling and repair of DNA single strand breaks. The PIONEER study is the first step towards exploring whether inhibitors of PARP-1, such as olaparib, may potentiate the anti-tumour effects of capecitabine-based chemo- radiation therapy.
The PIONEER study will explore the safety and toxicity of olaparib in combination with chemo - radiation in patients and aims to recommend a dose of olaparib for subsequent clinical trials. The PIONEER study will also will determine the pharmacodynamic effects of this novel combination regimen in patient blood and tumour (where available), and will explore anti-tumour efficacy.
These results will form the basis of randomised phase II studies comparing this regimen with capecitabine-based chemo-radiation in patients with locally advanced inoperable PDAC, and (separately) in patients with "borderline" resectable disease.