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 thepancreas. (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 hepaticartery).

• no tumor contact with the superior mesentery vein or portal vein or ≤180° contactwithout vein contour irregularity.

• adequate major organ functions

• Women of childbearing potential (including women with chemical menopause or nomenstruation for other medical reasons) must agree to use contraception from thetime ofinformed consent until 6 months or more after the last dose ofinvestigational products. Also, women must agree not to breastfeed from the time ofinformed consent until 6 months or more after the last dose of the investigationalproduct.

• Men must agree to use contraception from the start of study treatment until 3 monthsor more after the last dose of the investigational product.

• Participants must have signed written informed consent form in accordance withregulatory and institutional guidelines.

Exclusion Criteria:

• presence of clinically significant co-morbid medical conditions within 4 weeks priorregistration judged by Investigators

• severe arterial thromboembolic events (myocardial infarction, unstable anginapectoris, stroke) in past 6 months

• New York Heart Association class III or IV congestive heart failure, ventriculararrhythmias 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 ormanagement of suspected treatment-related pulmonary toxicity within 28 days prior toregistration

• 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 acquiredimmunodeficiency syndrome

• prior or concurrent malignancies within the last 3 years, with the exception ofcarcinoma in situ of the cervix, or basal type skin cancer

• any major surgery within 4 weeks of study treatment. Participants must haverecovered 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 enzymeinducers/inhibitors and/or strong UGT1A inhibitors

• known hypersensitivity to any of the components of study drugs