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

Trial details

Who runs it

Amsterdam UMC

Trial code

EU 2023-509463-24-01

Record updated

2025. január 9.

Original description

To determine the progression free survival (PFS) benefit of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma, or progression within 6 months of adjuvant gemcitabine treatment.Read full original descriptionShow less

To determine the progression free survival (PFS) benefit of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma, or progression within 6 months of adjuvant gemcitabine treatment.

Inclusion: 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.

Exclusion: 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; 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; 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; 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.

EU CTIS 2023-509463-24-01