Perioperative NALIRIFOX (liposomal Irinotecan in Combination with Fluorouracil, Leucovorin, and Oxaliplatin) in Resectable Pancreatic Adenocarcinoma: Randomized Phase II Trial

Inclusion Criteria: * previously untreated, histologically or cytologically proven PDAC * age between 20 and 75 years at registration * ECOG performance status of 0 or 1 * AJCC (8th edition) clinical stage I or II with measurable disease (CT or MRI) in the pancreas. (positron emission tomography scan alone not allowed) * Surgically resectable disease according to NCCN criteria (Version 1.2023 - May 4, 2023): * no arterial tumor contact (celiac axis, superior mesentery artery, or common hepatic artery). * no tumor contact with the superior mesentery vein or portal vein or ≤180° contact without vein contour irregularity. * adequate major organ functions * Women of childbearing potential (including women with chemical menopause or no menstruation for other medical reasons) must agree to use contraception from the time ofinformed consent until 6 months or more after the last dose of investigational products. Also, women must agree not to breastfeed from the time of informed consent until 6 months or more after the last dose of the investigational product. * Men must agree to use contraception from the start of study treatment until 3 months or more after the last dose of the investigational product. * Participants must have signed written informed consent form in accordance with regulatory and institutional guidelines. Exclusion Criteria: * presence of clinically significant co-morbid medical conditions within 4 weeks prior registration judged by Investigators * severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in past 6 months * New York Heart Association class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure or known abnormal electrocardiogram (ECG) with clinically significant abnormal findings in past 6 months * interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity within 28 days prior to registration * presence of diarrhea ≥ CTCAE v.5.0 grade 2 * concomitant systemic infection requiring treatment * prior organ allograft or allogeneic bone marrow transplantation * known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome * prior or concurrent malignancies within the last 3 years, with the exception of carcinoma in situ of the cervix, or basal type skin cancer * any major surgery within 4 weeks of study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 4 weeks before study treatment. * pregnant women or nursing mothers, or positive pregnancy tests * severe mental disorder * current use or any use in past 2 weeks of strong cytochrome P450 3A4 enzyme inducers/inhibitors and/or strong UGT1A inhibitors * known hypersensitivity to any of the components of study drugs