Background: As of today, the recommendation for patients with adenocarcinoma of the pancreas and hepatic metastases is systemic chemotherapy alone regardless of the number and location of metastases. In the past, case reports have repeatedly reported survival data of patients who received metastatic and primary tumor resection outside the guidelines. However, there are currently no controlled clinical data from prospective studies that have evaluated the effectiveness of systemic chemotherapy in combination with tumor and metastasis resection in the context of hepatic oligometastasis in pancreatic cancer. Methods: In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. Inclusion criteria are patients with a maximum of 5 liver metastases and histology proven PDAC. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (Nal-IRIFOX) was chosen as neoadjuvant chemotherapy since recent data suggested superior efficacy and less toxicity compared to mFOLFIRINOX. The primary endpoint is overall survival (OS) after R0/R1 resection. Secondary efficacy endpoints are R0/R1 resection rate and progression-free survival (PFS). Secondary safety endpoints are type, frequency and severity of adverse events with severity according to NCI CTCAE version 5.0 and perioperative morbidity and mortality. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant combination chemotherapy in cycles of 14 days for a duration of 16 weeks in total. In patients with progressive disease during or after the first 4 cycles, neoadjuvant chemotherapy will be permanently discontinued. Patients with tumor response or stable disease after the first 4 cycles according to RECIST v1.1 but a non-resectable primary tumor will receive 4 more cycles. Patients with tumor response or stable disease and a resectable primary tumor after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumor and hepatic metastases, if feasible. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. The study is currently ongoing on 11 high-volume centers for pancreatic surgery within Germany. This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Clinical trial information: NCT04617457.