Second Line Treatment With Nal-IRI and S1 in Pancreatic Cancer

Inclusion Criteria:

Subjects must satisfy all of the following inclusion criteria to be enrolled in the study.

1. Able to understand and provide written informed consent
2. ≥ 18 years of age
3. Histologically or cytologically confirmed adenocarcinoma of pancreas
4. Documented metastatic disease, according to RECIST 1.1.
5. Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine based treatment
6. Adequate hepatic, renal and hematological function

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)
2. Severe renal impairment (CLcr ≤ 30 ml/min)
3. Inadequate bone marrow reserves as evidenced by:

   1. ANC ≤ 1,5 x 10 9 /L; or
   2. Platelet count ≤ 100 x 10 9 /L;
4. WHO/PS 0-1
5. Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment
6. Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea \> grade 1
7. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
8. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
9. Active infection or an unexplained fever \>38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health
10. Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
11. Known hypersensitivity to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
12. Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
13. Previous treatment with fluoropyrimidine therapy
14. Known dihydropyrimidine dehydrogenase (DPD) deficiency
15. Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of liposomal irinotecan (Nal-IRI).

Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.