A Phase II Trial to Assess the Evolution of KRAS Mutation Load by Liquid Biopsy in Patients With Resectable Pancreatic Ductal Adenocarcinoma Treated With Neoadjuvant NALIRINOX

Date de début de l'étude : 1 mai 2019

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.