Purpose of the study Phase I study: to explore the optimal dose combination of irinotecan liposome + oxaliplatin + bevacizumab regimen, irinotecan liposome + oxaliplatin Phase II study: to evaluate the safety and efficacy of the second-line treatment regimen of irinotecan liposome combined with oxaliplatin and bevacizumab compared to the second-line treatment regimen of irinotecan liposome combined with 5-FU/LV in advanced pancreatic cancer Sample size 138 cases Phase I Crawl, sample size 9-18 cases. Phase II randomized controlled clinical study, historical data NAPOLI-1 study, ORR of 8.8% for irinotecan liposome + 5-FU/LV, planned trial arm ORR upgrade to 25%, calculated at 60 cases in each arm.
Subject population Patients with advanced pancreatic cancer diagnosed after failure of first-line therapy, confirmed by histopathology or cytopathology, who meet the inclusion criteria and do not meet the exclusion criteria.
Phase I design:
Liposomal irinotecan + oxaliplatin + bevacizumab, 2-week regimen Liposomal irinotecan: start exploring with 50mg/m2 dose, preset 50mg/m2, 60mg/m2, 2 dose groups, 90min IV infusion, d1; Oxaliplatin: explored from 60mg/m2 dose, preset 60mg/m2, 85mg/m2, 2 dose groups, IV infusion, d1; Bevacizumab: 5 mg/kg, i.v., d1; Phase II study design.
Trial group:
Irinotecan liposomal: RP2D, i.v., 90min, d1; Oxaliplatin: RP2D, i.v., d1; Bevacizumab: 5mg/kg, i.v., d1; Cycles every 2 weeks until disease progression or intolerable; imaging every 3 treatment cycles/1.5 months.
Control:
Liposomal irinotecan: 70 mg/m2 IV for 90 min, d1; Calcium folinate: 400 mg/m2, IV infusion over 30 min, d1; 5-FU: 2400 mg/m2, continuous IV infusion over 46h; Cycles every 2 weeks until disease progression or intolerable; imaging every 3 treatment cycles/1.5 months.
Notes:
If the duration of irinotecan liposome infusion can be extended appropriately based on the patient\'s clinical response; if the patient withdraws from the trial due to intolerance of toxicity (e.g., neurotoxicity or myelotoxicity) induced by one of the drugs, follow up is required until PFS and OS.
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