Intensified treatment in patients with local operable but oligometastatic pancreatic cancer - multimodal surgical treatment versus systemic chemotherapy alone: a randomized controlled trial [AIO-PAK-0219 METAPANC]

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Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive cancer entity and initially presents in more than 60% of the patients with metastasis. In the last years systemic therapy with the FOLFIRINOX protocol (Oxaliplatin, Irinotecan, 5-FU) has demonstrated as an effective therapy with increased survival and response rates above 30 % with tumor regression up to complete responses. However, recurrence of disease or secondary resistance inevitably occur leading to an overall survival of only approximately 11 months. In the group of metastasized PDACs a subgroup of patients presents with oligometastasized disease with a maximum of three liver metastases in a synchronous or metachronous fashion, though there is no consensus definition. As in other gastrointestinal cancers there might exist a potential curative window of opportunity for such patients including surgery. Thus, while continued chemotherapy usually in a de-escalated fashion due to toxicity of FOLFIRINOX is the standard of care, surgical resection of the primary cancer and the metastases may be offered to patients. However, the relevance of surgery in oligometastasized patients is unclear up to now and many patients in such context are treated individually in Europe. There exist neither prospective data nor data from controlled randomized clinical trials worldwide. In the applied prospective randomized phase-III trial (METAPANC) the relevance of surgical resection of the primary cancer and the metastases after induction chemotherapy with FOLFIRINOX will be investigated. Only patients with tumor regression or stable disease after at least 4 months of chemotherapy will be included. Only patients in whom a curative and complete resection of the primary and the metastases can be achieved (experimental arm) will be randomized. The standard arm consists of a 4-months chemotherapy (FOLFIRINOX) followed by a de-escalating chemotherapy (standard of care). The primary endpoint is overall survival. This prospective randomized trial is accompanied by a translational research program including the central sampling and molecular characterization of tumor tissue, liquid biopsy and radiomics approaches. Despite the increasing incidence of PDAC the number of oligometastatic patients eligible for this trial is small and defines it as ”rare disease“. Therefore, the largest German Hospitals (AIO/ACO Studie) and the Dutch Pancreatic Cancer Group (DPCG) as well as a two northern European centers (Oslo/NOR and Helsinki/FIN) will recruit patients in this trial. The study groups in the three countries have expressed their strong interest for this trial. We envision practice-changing results upon successful completion of the phase III trial with respect to the inclusion of surgical resection in multimodal regimens for selected patients with oligometastatic PDAC.