Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG (CASSANDRA TRIAL)

1. Cyto/histological diagnosis of pancreatic ductal adenocarcinoma*;

2. Clinical stage I-III disease according to TNM 8th Ed. 2017 [appendix 1];

3. Resectable or borderline resectable disease, as anatomically defined according to NCCN Guidelines Version 1.2020 - Pancreatic Adenocarcinoma [appendix 2] and biologically defined according to the International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017 (CA 19.9 > 500 IU/ml) (Isaji et al., 2018);

4. Karnofsky Performance Status > 60% [appendix 3];

5. Age 18 and ≤ 75 years;

6. Adequate bone marrow function (GB ≥ 3500/mm3, neutrophils ≥1500/mm3, platelets ≥ 100000/mm3, Hb ≥10 g/dl);

7. Adequate kidney function (serum creatinine < 1.5 mg/dL);

8. Adequate liver function (ALT and AST < 3 ULN and Serum total bilirubin ≤ 1.5 ULN);

9. No prior treatment (chemotherapy, radiotherapy and/or surgery) for pancreatic cancer;

10. Women must not be on pregnancy or lactation;

11. Patient of child-bearing potential must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for a minimum of the following 6 months; this applies to patients of both sexes. [appendix 4];

12. Patient information and signed written informed consent.

1. Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and other periampullary malignancies.

2. Prior or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin and of other neoplasms without evidence of disease at least from 5 years;

3. Symptomatic duodenal stenosis;

4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment

5. Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications

6. Clinical stage IV (including ascites or malignant pleural effusion) disease according to TNM 8th Ed. 2017 [appendix 1];

7. Locally advanced disease according to NCCN Guidelines Version 1.2020 - Pancreatic Adenocarcinoma [appendix 2];

8. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. These include, but are not limited to:

9. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study

10. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

11. Any condition that confounds the ability to interpret data from the study

12. Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up;

13. Pre-existing neuropathy, Gilbert's disease or genotype UGT1A1 * 28 / * 28.

14. mutation in DPYD

15. Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine.

16. Concurrent treatment with other experimental drugs;

17. Fructose intolerance.