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. Translated with DeepL.com (free version)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
138
Exploration started with 50mg/m\^2 dose, preset 50mg/m\^2, 60mg/m\^2, 2 dose groups, IV infusion 90min, d1
Exploration started with 60mg/m\^2 dose, preset 60mg/m\^2, 85mg/m\^2, 2 dose groups, IV infusion, d1
5mg/kg,i.v.,d1
2400mg/m\^2, i.v.,46h
400mg/m\^2, i.v.,d1
70mg/m\^2, i.v.,d1
Phase II recommended dose
Phase II recommended dose
Beijing
Beijing, China
NOT_YET_RECRUITINGChinese PLA General Hospital
Beijing, China
RECRUITINGTo explore the optimal dose combination of irinotecan liposomes plus oxaliplatin in the regimen of irinotecan liposomes plus oxaliplatin in bevacizumab
The DLT determination criteria are as follows: 1. Hematologic toxicity: * Grade 4 neutropenia with application of granulocyte colony-stimulating factor still persisting for \>3 days ; * Grade 3 or above FN; * Grade 3 thrombocytopenia with bleeding and/or need for blood transfusion; * Grade 4 thrombocytopenia; * Grade 4 anemia. 2. Non-hematologic toxicity: ≥ Grade 3 non-hematologic toxicity, except: ① Transient (≤24 hours) Grade 3 fever (\>40°C), Grade 3 malaise, Grade 3 headache, Grade 3 nausea, which recovers to Grade 1 or baseline after treatment; Grade 3 vomiting, Grade 3 electrolyte disorders (including hypokalemia, hypophosphatemia, hypocalcemia, etc.), recovery to Grade 1 or baseline within 48 hours after treatment.
Time frame: At the end of Cycle 1 (each cycle is 14 days)
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