Pancreatic Resectability in Cancers With Known Limited Extension (PRICKLE)

This is a single-centre, non-randomised, phase 2a, single arm, Simon two-stage design trial of nab-paclitaxel and gemcitabine (ABX/GEM) in patients with histological documentation of pancreatic ductal adenocarcinoma (PDAC) who are determined by central radiological review to have "category 2" borderline unresectable LAPC. We will investigate the feasibility of administering ABX/GEM in terms of safety and efficacy, and will study activity both in terms of radiological response and the feasibility of downstaging patients to "category 1" status, in order to attempt resection after up to 6 cycles of combination treatment. In addition to adding to data on the safety and tolerability of this combination, peri- and post-operative morbidity following this treatment will be evaluated. As part of the trial, detailed correlative studies will be undertaken to evaluate the mechanism of action of the combination, at a tissue level, a circulating biomarker level and a radiological level. We propose that the tumour shrinkage (response) seen in Stage IV pancreatic cancer patients as a result of ABX/GEM may translate to a realistic prospect of downstaging borderline unresectable LAPC tumours sufficiently to enable resection. Notionally, even in the absence of a classical partial response by RECIST criteria (≥30% reduction in sum of longest diameters) a beneficial outcome may arise from any tumour shrinkage sufficient to permit the tumour to be separated from major vessels thus rendering it resectable. Such an outcome may significantly alter the poor survival outcomes in this group of patients. The PRICKLE clinical study paradigm is useful for evaluating novel agents and combinations that show impressive activity in the pre-clinical or advanced setting and offers an opportunity for detailed correlative translational studies to evaluate activities of therapy.