The goal of this clinical trial is to learn if surufatinib (VEGFR-TKI) plus toripalimab (PD-1 inhibitor) and mFOLFIRINOX (chemotherapy) works as neoadjuvant therapy for patients with high-risk or borderline resectable pancreatic cancer. It will also learn about the safety of the combination regimen. The main questions it aims to answer are: Does the treatment regimen of surufatinib combined with immunotherapy and chemotherapy could provide further survival benefits for patients with high-risk resectable or borderline resectable pancreatic cancer as neoadjuvant therapy? Is the safety of this combination therapy tolerable? Participants will: Take surufatinib (200mg, qd, po, q2w), Toripalimab (3mg/kg, iv, d1, q2w), Oxaliplatin (68 mg/m², iv, d1, q2w), Irinotecan (135 mg/m², iv, d1, q2w), Calcium folinate (400 mg/m², iv, d1, q2w), 5-FU (2400 mg/m², iv). Treatment for up to 8 cycles. Visit the clinic once every 8 weeks (± 7 days) for checkups and tests. Keep a diary of their symptoms and record daily medication doses.
This study is a single-center, single-arm, phase II study. Preoperative neoadjuvant treatment plan: * Surufatinib: 200 mg orally once daily, continuous dosing, with a 14-day treatment cycle; * Toripalimab: 3 mg/kg per dose, intravenous infusion over 1 hour on day 1, every 14 days per treatment cycle; * Oxaliplatin: 68 mg/m² intravenous infusion over 2 hours on day 1; * Irinotecan: 135 mg/m² intravenous infusion over 30-90+ minutes on day 1; * Calcium folinate: 400 mg/m² intravenous infusion over 2 hours on day 1; * 5-FU: 2400 mg/m² continuous intravenous infusion over 46 hours; repeated every 14 days per treatment cycle. Neoadjuvant treatment will be administered for up to 8 cycles. During treatment, tumor assessments using imaging will be conducted every 8 weeks (±7 days). For patients achieving stable disease, partial response, or complete response, it will be evaluated whether surgery is feasible. Surgery should occur at least 2 weeks after the last neoadjuvant treatment. Postoperative adjuvant treatment plan: * Adjuvant treatment will begin within 4-8 weeks after surgery, with the specific regimen determined by the investigator. * During postoperative adjuvant treatment, tumor assessments using imaging will be conducted every 8 weeks (±7 days) until disease progression (RECIST 1.1) or death (during patient treatment), or until intolerable toxicity occurs. Subsequent treatment after disease progression and survival status will also be recorded.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Surufatinib: 200 mg orally once daily, continuous dosing, with each 14 days as one treatment cycle
Toripalimab: 3 mg/kg per dose, intravenous infusion over 1 hour, on day 1, with each 14 days as one treatment cycle
Oxaliplatin: 68 mg/m² intravenous infusion over 2 hours, on day 1; Irinotecan: 135 mg/m² intravenous infusion over more than 30-90 minutes, on day 1; Calcium folinate: 400 mg/m² intravenous infusion over 2 hours, on day 1; 5-FU: 2400 mg/m² continuous intravenous infusion over 46 hours; With each 14 days as one treatment cycle; Neoadjuvant treatment for up to 8 cycles.
Sun Yat-sen University Cancer Center
Guangzhou, China
12-month Event Free Survival Rate
Event-free survival (EFS) is defined as the time from enrollment to the first occurrence of any of the following events, including (1) disease progression according to RECIST criteria, (2) undergoing R2 resection surgery, (3) disease recurrence after surgery, or (4) death from any cause. The 12-month EFS rate is defined as the proportion of patients among the total enrolled who have not experienced any of the above predefined events within 12 months from enrollment.
Time frame: From enrollment to the end of observation at 12 months
R0 Resection Rate
The proportion of patients whose postoperative pathological evaluation shows no residual tumor cells at all surgical margins (R0) among all patients who underwent surgery after receiving neoadjuvant therapy.
Time frame: From enrollment to the end of treatment for up to 16 weeks
Objective Response Rate
Refers to the proportion of patients whose tumors shrink by a certain amount and maintain it for a certain period of time, including cases of CR and PR. The objective response rate is evaluated using the RECIST 1.1. Subjects must have measurable tumor lesions at enrollment, and the efficacy evaluation criteria according to RECIST 1.1 are classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Time frame: From enrollment to the end of treatment for up to 16 weeks
Disease Control Rate
Refers to the percentage of patients with complete response, partial response, and stable disease maintained for more than 4 weeks among those evaluable for efficacy.
Time frame: From enrollment to the end of treatment for up to 16 weeks
Recurrence Free Survival
Recurrence-free survival (RFS) refers to the time interval from the date of surgery following neoadjuvant therapy to the recurrence of the tumor (including local/regional recurrence or distant metastasis) or death from any cause.
Time frame: From the date of surgery at week 18 to the recurrence of the tumor or death for up to 96 weeks.
Overall Survival
Overall survival (OS) refers to the time from enrollment to the date of death from any cause.
Time frame: From enrollment to the date of death from any cause for up to 96 weeks.
AEs
Collect adverse events (AEs) from enrollment to 30 days after the end of treatment, and grade the AEs according to CTCAE 5.0.
Time frame: From enrollment to 30 days after the end of treatment at 16 weeks
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