A randomized phase II study of second line treatment with liposomal irinotecan and S1 versus liposomal irinotecan and 5-fluorouracil in patients with metastatic pancreatic cancer who failed on first line gemcitabine-based chemotherapy

Prior treatment

• Current use or any use in last two weeks of strong CYP2A6- enzyme inhibitors, CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
• Previous treatment with fluoropyrimidine therapy
• Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.

Other illness

• Known hypersensitivity to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
• Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
• Severe renal impairment (CLcr ≤ 30 ml/min)
• Any clinically significant disorder impacting the risk-benefit balance negatively per physician’s judgment
• Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
• Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
• Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician’s opinion might compromise the patient’s health

Lab values

• Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)
• 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).
• Inadequate bone marrow reserves as evidenced by: a. ANC ≤ 1,5 x 10 9 /L; or b. Platelet count ≤ 100 x 10 9 /L;

Other

• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• or male patients: unwilling to use contraception during treatment and 4 months following last dose of Nal-IRI and 6 months after S-1
• Contraception required for 6 months following the last dose of S-1
• WHO/PS 2 or higher

• Able to understand and provide written informed consent
• ≥ 18 years of age
• Histologically or cytologically confirmed adenocarcinoma of pancreas
• Documented metastatic disease, according to RECIST 1.1.
• Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine based treatment
• Adequate hepatic (serum bilirubin total between 0-17 μmol/L, AST between 0-40 U/L, ALT between 0-34 U/L, renal (creatinine between 65-95 μmol/L) and hematological (hemoglobin between 7.5-10 mmol/L, platelets between 150-400 10E9/L, leukocytes between 4.0-10.5 10E9/L) function