PIONEER Study
Research type
Research Study
Full title
PIONEER: A Phase I Study of Olaparib in Combination with Chemo-radiation in Locally Advanced Pancreatic Cancer
IRAS ID
159690
Contact name
Jeff Evans
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Eudract number
2014-002074-37
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Infiltrative ductal adenocarcinoma of the pancreas is the fifth commonest cancer and the fourth commonest cause of cancer deaths in the UK. Approximately 30% of patients present with locally advanced, un-resectable, non-metastatic disease. Despite advances in chemo-radiation and in systemic chemotherapy agents, most patients ultimately develop local disease progression and / or distant metastases, with a disappointing median survival ranging from 5 to 11 months. Consequently, novel effective therapies are urgently required in this disease.
Poly (ADP-ribose) polymerases (PARP) are a family of highly conserved enzymes with a critical role in DNA repair. There is a wealth of preclinical data, both in vitro and in vivo, to support the notion that inhibition of PARP-1 will potentiate the cytotoxicity of DNA-damaging agents, including radiation. Consequently, we hypothesise that the addition of a PARP inhibitor to a chemo-radiation backbone might potentiate the effects of this combined modality therapy in patients with both locally advanced, inoperable pancreatic cancer as well in those with “borderline resectable” disease.
We propose a phase I, open-label, non-randomised, multi-centre, dose escalation study of the PARP inhibitor, olaparib, administered in combination with standard capecitabine – based chemo-radiation combined modality therapy in patients with locally advanced, inoperable pancreatic ductal adenocarcinoma. The objectives of this study are to explore the safety and toxicity of this regimen, to identify the dose-limiting toxicities and the maximum tolerated dose, and to recommend a dose of olaparib for phase II clinical trials. Once the recommended dose has been determined, an additional cohort of 12 patients with “borderline” resectable pancreatic ductal adenocarcinoma will be recruited to determine the feasibility of recruiting patients into a trial of “neo-adjuvant” chemo-radiation therapy, to determine the tolerability of this regimen in this patient population, and to potentially down-stage their disease.REC name
Scotland B REC
REC reference
15/SS/0011
Date of REC Opinion
3 Mar 2015
REC opinion
Further Information Favourable Opinion