Trial to Investigate Intensified Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

This is a prospective open randomized multicenter phase II trial with two arms. Patients suffering from histologically confirmed LAPC (and assessed as unresectable or borderline resectable according to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines "pancreatic adenocarcinoma" version 1.2013) without metastases will receive two different neoadjuvant treatment regimens: First all patients receive two cycles Gem/nab-PAC (duration of each cycle 28 days) as neoadjuvant chemotherapy in equal measure and a first restaging is performed after these two cycles based on imaging criteria. If there is no progression according to Response evaluation criteria in solid tumors (RECIST 1.1) criteria at the first restaging, the patients are randomized in a 1:1 relation to: Two further cycles Gem/nab-PAC (duration of each cycle 28 days). or Four further cycles FOLFIRINOX (duration of each cycle 14 days). After the neoadjuvant chemotherapy a 2nd restaging is performed based on imaging criteria. All patients without progression at this restaging or at an earlier time point undergo obligatory exploratory laparotomy irrespective of imaging criteria to assess resectability. If they are evaluated as converted to resectable during this exploratory laparotomy, pancreas resection in curative intent will be performed. All patients with successful R0 or R1 pancreatic resection will receive three further cycles adjuvant chemotherapy with Gem/nab-PAC. Adjuvant chemotherapy will start within 4 to 8 weeks after pancreatic resection surgery. Further treatment of patients with PD after 1st or 2nd restaging as well as patients with unresectable status based on exploratory laparotomy is under the discretion of the local investigators (e.g. second-line chemotherapy in case of distant relapse or local radiochemotherapy in case of local progression or definitive irresectability). All patients are followed up for local recurrence, progression and survival until death or for at least one year after last application of study drugs whichever is sooner. The translational research conducts exploratory analyses for potential biomarkers of possible prognostic or predictive value for efficacy of neoadjuvant chemotherapy in LAPC; including analyses of circulating tumor cells, molecular pathways of pancreatic adenocarcinoma including SPARC expression.