Open-label, Single Arm Phase II Trial Investigating the Efficacy, Safety and Quality of Life of Neoadjuvant Chemotherapy With Liposomal Irinotecan Combined With Oxaliplatin and 5-Fluorouracil/Folinic Acid Followed by Curative Surgical Resection in Patients With Hepatic Oligometastatic Adenocarcinoma of the Pancreas
This is an interventional, open-label, non-randomised, multicentre, single-arm phase II clinical trial. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant combination chemotherapy (liposomal irinotecan, oxaliplatin, 5-fluouracil, folinic acid (NAPOX)) in cycles of 14 days. Patients with tumour response or stable disease and a resectable primary tumour after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumour and hepatic metastases, if feasible; these patients may receive 4 more cycles of neoadjuvant chemotherapy 2-4 weeks after the explorative laparotomy if the surgeon rated the primary tumour as non-resectable during the explorative laparotomy.
• Histologically confirmed diagnosis of treatment-naïve limited hepatic metastatic adenocarcinoma of the pancreas Definition of limited hepatic metastasis: 1 to 5 metastases in CT/MRI and/or contrast-enhanced ultrasound scan, which are potentially resectable or treatable by ablative procedures (Note 1: Patients also fulfil this inclusion criterion if a hepatic metastasis was partly or entirely removed as part of the diagnosis and is thus not detectable by CT/MRI and/or contrast-enhanced ultrasound scan at screening. Note 2: If more than 5 metastases are unexpectedly detected during surgery, it is not a violation of this inclusion criterion if the excess metastases had not been detectable by CT/MRI and/or contrast-enhanced ultrasound scan at screening.)
• Measurable disease according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate renal, hepatic and bone marrow function, defined as
‣ Calculated creatinine clearance ≥60 mL/min
⁃ Total bilirubin ≤2 mg/dL; patients with biliary stent may be included if bilirubin level decreased to ≤2 mg/dL after stent insertion
⁃ alanin-aminotransferase and aspartat-aminotransferase (ALT and AST) ≤5 × upper limit of normal (ULN)
⁃ Absolute neutrophil count (ANC) ≥1.5 × 109/L
⁃ Thrombocytes ≥100 × 109/L
⁃ Haemoglobin ≥9 g/dL
⁃ activated partial thromboplastin time (aPTT) ≤1.5 × ULN and Quick value ≥70%
• Patients ≥18 years at the time of signing the informed consent
• Females of childbearing potential (FCBPs) must agree to use highly effective contraceptive measures (Pearl index \<1) or practice true abstinence from any heterosexual intercourse for the duration of treatment and for at least 1 month after the last IMP administration (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient). A woman will be considered as being of childbearing potential unless she is at least 50 years old and, moreover, has gone through menopause for at least 2 years or has been surgically sterilised.
• Males must agree to use condoms or practice true abstinence from any heterosexual intercourse for the duration of IMP treatment and at least 6 months after the last IMP administration (true abstinence is acceptable if this is in line with the patient's preferred and usual lifestyle). Male patients must furthermore refrain from donating sperm during the clinical trial until at least 6 months after the last IMP administration.
• Patient's written informed consent prior to any trial-specific procedure
• Patient's legal capacity to consent to participation in the clinical trial