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)
Age 18 to 75 years old;
Patients with pancreatic cancer diagnosed by histopathology or cytology;
Unresectable disease assessed by multidisciplinary and imaging;
Subjects who have received prior failed first-line therapy, and recurrence within 6 months of the end of (neo)adjuvant therapy is considered a first-line treatment failure;
Patients who have had other malignant tumors within the previous 5 years (except cured carcinoma in situ and basal cell carcinoma of the skin);
Uncontrollable pleural effusion or ascites;
Any known brain metastasis or meningeal metastasis;
Concomitant use of a potent CYP3A4 inducer within 3 weeks prior to the first dose, or concurrent use of a potent CYP3A4 inhibitor or potent UGT1A1 inhibitor within 3 weeks prior to the first dose;
Parallel
Irinotecan liposoma
DrugExploration started with 50mg/m\^2 dose, preset 50mg/m\^2, 60mg/m\^2, 2 dose groups, IV infusion 90min, d1
oxaliplatin
DrugExploration started with 60mg/m\^2 dose, preset 60mg/m\^2, 85mg/m\^2, 2 dose groups, IV infusion, d1
bevacizumab
Drug5mg/kg，i.v.，d1
5-FU
Drug2400mg/m\^2, i.v.，46h
LV
Drug400mg/m\^2, i.v.，d1
Irinotecan Liposomal
Drug70mg/m\^2, i.v.，d1
Irinotecan Liposomal
DrugPhase II recommended dose
Oxaliplatin
DrugPhase II recommended dose
To 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.
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Dai, Guanghai
Lead sponsor
Chinese PLA General Hospital
Sponsor institution
