Predictive Value of Transcriptome-based OncoTreat/Oncotarget and Organoid Testing in Metastatic Pancreatic Cancer.

Primary objective. The study seeks primarily to demonstrate whether a significant correlation between the IVD based predicted drug sensitivity and the patient's progression-free survival (PFS) in metastatic pancreatic adenocarcinoma after administered standard therapies (which are not chosen based on the test) exist. Secondary objectives. The study seeks further to 1. Explore the correlation between Darwin-test predicted drug sensitivity and patient-derived PDO sensitivity to clinically used drug regimens. 2. Explore the correlation between the measured PDO sensitivity to the administered standard therapies and the clinical course of the patient, i.e. PFS (in vivo and in vitro comparison). 3. Collect samples for biobanking and future identification of potential new markers associated with tumor response. Safety objectives. The study aims to assess: The rate and severity of 30-days post-operative surgical complications related to laparoscopic surgical biopsy required to retrieve tumoral tissue for IVD-based testing and PDO generation. The primary outcome is achieved if a significant correlation between IVD based predictions of drug sensitivity and clinically observed patient outcome (progression-free survival after administered standard therapy) exist. The secondary outcomes are achieved if 1. There is a significant correlation between Darwin-test predicted drug sensitivity and patient-derived PDO sensitivity to clinically used drug regimens. 2. There is a significant correlation between the measured PDO sensitivity to the administered standard therapies and the clinical course of the patient, i.e. PFS (in vivo and in vitro comparison). Biobanked samples will be retrospectively analysed to highlight potential biochemical markers of tumour response to therapy if attributable. The safety outcome will assess descriptively the rate of severe surgical post-operative complication related to laparoscopic surgical biopsy required to retrieve tumoral tissue for IVD-testing and PDO generation and occurring within 30 postoperative days. Non-Interventional, single arm, observational study Inclusion criteria: * Informed Consent as documented by signature * Patients older than 18 years * Patients with metastatic pancreatic ductal adenocarcinoma * At least one lesion amenable for surgical excisional biopsy * ECOG Performance status 0-2 * Radiologically measurable disease * Life expectancy \> 3 months * Absolute leucocyte count \>1.5 G/l, platelets \>100 G/l * Serum creatinine \<1.5 times of the upper limit of normal or Clearance \>50ml/min (according to the CKD-EPI formula) Exclusion criteria: * Known allergies or intolerance to one or more compounds present in one of the first line or second line regimens * Concomitant need for full anticoagulation that cannot be interrupted or bridged prior to tissue biopsy * ECOG PS \>2 * Heart failure (NYHA class III-IV) * Severe or uncontrolled concurrent illness * Active viral infection from HIV, HBV or HCV, even if under antiretroviral treatment * Myocardial infarction within the previous 6 months * Patients who are pregnant or breastfeeding