• R0 resection [ Time Frame: Through the study completion (estimated to be 15 months) ]
• 1-year survival and Overal survival (OS) in baseline KRAS+ and KRAS- subjects [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Progression Free Survival (PFS) [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Assessment of the proportion of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Assessment of the number of KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Impact on R0 resection for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Impact on histological tumour response for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Impact on PFS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Impact on 1-year survival for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Impact on OS for KRAS- subjects switching to KRAS+ (and from KRAS+ to negative) after neoadjuvant NALIRINOX [ Time Frame: Through the study completion (estimated to be 15 months) ]
• Number of AEs and SAEs (according to CTCAE) to describe the safety profile of the neoadjuvant NALIRINOX scheme [ Time Frame: Through the study completion (estimated to be 15 months) ]

Pancreatic cancer has an unfavorable prognosis with a reduced possibility of long-term survival. The only treatment with curative potential is surgery, but it is only possible in 15-20% of cases.

There are patients with clear criteria for surgical entry, others at the limit of the possibility of surgery, and patients with such advanced disease (either locally or with metastasis) that surgery is not indicated.

The objective of neoadjuvant chemotherapy treatment (received before surgery) is to reduce the tumor before surgery and reduce the risk of subsequent metastases and local recurrences, in borderline tumors or those resectable with high-risk criteria.

The FOLFIRINOX scheme, composed of 5-fluorouracil / folinic acid, oxaliplatin and irinotecan, is recommended as neoadjuvant treatment, but the response is still low. This study will use a modified FOLFIRINOX (NALIRINOX) regimen with a form of irinotecan attached to liposomes that allows greater action on tumor cells.

Mutations in the KRAS gene are associated with a greater growth capacity of tumor cells and are present in 90% of pancreatic cancers in advanced stages. They would be less frequent in earlier phases but little is known about the impact that chemotherapy treatment and subsequent surgery could have on the increase or decrease of these mutations, as well as their implication. The follow-up of these mutations with repeated pancreatic biopsies is not viable, but it can be monitored by simple blood samples in which the genetic material of the tumor can be analyzed.

Inclusion Criteria:

1. Male or females, aged 18 years or older
2. Histologically or cytologically confirmed diagnosis of PDAC
3. Candidates for pancreatic cancer surgery (no comorbidities that can exclude for surgery)
4. Life expectance of at least 12 months
5. Carbohydrate antigen 19-9 (CA19-9) levels < 500 U/ml
6. ECOG performance status ≤ 1

7. Adequate bone marrow function:

   • Hemoglobin >9 g/dL
   • Platelets >100.000 µL
   • Absolute neutrophil count (ANC) >1500 µl
   • Serum albumin > 3 g/dL

8. Adequate hepatic function:

   • Aspartate aminotransferase (AST) <3 upper limits of normal (ULN)
   • Alanine Aminotransferase (ALT) <3 ULN
   • Total Bilirubin < 1.5 ULN. If values are > 1.5 external drainage with a stent is allowed.

9. Adequate renal function:

   - Clearance of creatinine (ClCr) >60 ml/min

10. Sexually active men and women of childbearing potential must use efficient contraceptive methods. Contraceptive methods comprise: oral contraceptives, intrauterine devices, sexual abstinence, tubal ligation, IUD, barrier methods or another contraceptive considered appropriate by the investigator. Women of childbearing potential must have a negative serum pregnancy test before study entry.
11. Agree to participate and signed the ICF.

Exclusion Criteria:

1. Patients with metastatic disease
2. Patients ≥ 75 years.
3. Uncontrolled coagulopathy
4. Patients with a contraindication to surgery (locally advanced disease or patients not amenable to pancreatic surgery due to a previous comorbidity)
5. Patients with prior or concurrent malignant disease that required treatment with chemotherapy in the past.
6. Previous cytotoxic therapy within 36 months for other no-cancer disease (ie arthritis rheumatoid)
7. Known or suspected reactions to any component of the study medication (5-FU/LV, nal- IRI or oxaliplatin) or to components of similar chemical or biologic composition
8. Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule
9. Human immunodeficiency virus (HIV) positivity, active Hepatitis B or Hepatitis C infection.
10. Uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, myocardial infarction, or left ventricular ejection fraction (LVEF) < 50, among others, or psychiatric illness/social situations that would limit compliance with study requirements.
11. Pregnant or breast-feeding women.
12. Any medical condition that, based on investigator's criteria, places the subject at risk, makes the subject ineligible or may jeopardize protocol compliance.