The purpose of this research is to investigate the activity and safety of the combination of gemcitabine plus nab-paclitaxel and sintilimab as neoadjuvant therapy in treating patients with resectable and borderline resectable pancreatic cancer. The drugs involved in this study are: * Sintilimab * Nab-paclitaxel * Gemcitabine
Pancreatic cancer is a highly fatal disease with a 5-year survival rate of less than 5%, and it is becoming an increasingly common cause of cancer mortality. Neoadjuvant therapy, such as gemcitabine plus nab-paclitaxel, can effectively avoid the proliferation of residual tumors and reduce the risk of lymph node metastasis, implantation metastasis during surgery, and early relapse after operation. Most importantly, it can change the immune status by turning the "immune cold" pancreatic cancer into an "immune hot" condition, which will enable the application of immune checkpoint inhibitors. Sintilimab is an immune checkpoint inhibitor against programmed cell death protein 1, which is applicable for treatment of a range of cancers including non-small cell lung cancer, melanoma, esophageal cancer, and liver cancer. It could block the interaction between PD-1 and its ligands and help the anti-tumor effect of T cells to recover. The present study is intended to investigate the activity and safety of the combination of gemcitabine plus nab-paclitaxel and sintilimab as neoadjuvant therapy in treating patients with resectable and borderline resectable pancreatic cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Patients firstly receive sintilimab 200 mg (iv, 30 minutes) on day 1 for 3 weeks, followed by one week without treatment. Treatment repeats every 4 weeks for up to 3 circles in the absence of disease recurrence or unacceptable toxicity.
Patients firstly receive nab-paclitaxel 125 mg/m\^2 (iv, 30 minutes) on days 1, and 8 for 3 weeks, followed by one week without treatment. Treatment repeats every 4 weeks for up to 3 circles in the absence of disease recurrence or unacceptable toxicity.
Patients secondly receive gemcitabine 1000 mg/m\^2 (iv, 30 minutes) on days 1, and 8 for 3 weeks, followed by one week without treatment. Treatment repeats every 4 weeks for up to 3 circles in the absence of disease recurrence or unacceptable toxicity.
Zhongshan Hospital
Shanghai, Shanghai Municipality, China
2-year overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
To evaluate the overall survival of patients with resectable and borderline resectable pancreatic cancer treated with the combination of sintilimab and gemcitabine plus nab-paclitaxel. Outpatient visit, phone interview
Time frame: From date of enrollment to the date of death for any cause, assessed 2 months during therapy and 3 months thereafter up to 24 months
Overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
To evaluate the overall survival of patients treated with this regimen. Outpatient visit, phone interview
Time frame: From date of enrollment until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months
Event-free survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
To evaluate the event-free survival of patients treated with this regimen. Outpatient visit, phone interview
Time frame: From date of enrollment until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months
Objective response rate and disease control rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel
To evaluate the objective response rate and disease control rate of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Time frame: One month during therapy and 3 months thereafter up to 24 months
Recurrence-free survival after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
To evaluate the recurrence-free survival of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Time frame: One month during therapy and 3 months thereafter up to 24 months
Resection rate and R0 resection rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
To evaluate the resection rate and R0 resection rate of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Time frame: One month during therapy and 3 months thereafter up to 24 months
Major pathological response rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
To evaluate the major pathologic response rate of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Time frame: One month during therapy and 3 months thereafter up to 24 months
Node-negative resection rate, the occurrence rate and severity of perioperative complications after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
To evaluate the node-negative resection rate, the occurrence rate and severity of perioperative complications of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Time frame: One month during therapy and 3 months thereafter up to 24 months
Progression-free survival after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel, but being determined as unresectable after surgical exploration
To evaluate the progression-free survival of patients treated with this regimen, but determined as unresectable after surgical exploration. Outpatient visit, phone interview
Time frame: One month during therapy and 3 months thereafter up to 24 months
Number and severity of toxicities according to NCI CTCAE version 4.0
To evaluate the occurrence of toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0) in patients treated with this regimen. The toxicity profile includes but not limits neutropenia, thrombocytopenia, peripheral neuropathy, hypoglycemia, metabolic acidosis (acute or chronic, including ketoacidosis), which will be summarized as the percentage of patients by type and grade according to treatment group. Outpatient visit, phone interview, laboratory findings
Time frame: One week during therapy and 3 months thereafter up to 24 months
Correlation between patients' immunological parameters before and after the application of sintilimab and gemcitabine plus nab-paclitaxel and prognosis of them
To evaluate the correlation between status of immunological parameters (such as MSI, TMB, the expression of PD-1/PD-L1, and dMMR) and prognosis of patients treated with this regimen. Outpatient visit, laboratory findings
Time frame: One month during therapy and 3 months thereafter up to 24 months
Whole exome sequencing before and after the application of sintilimab and gemcitabine plus nab-paclitaxel
To evaluate difference of the whole exome sequencing before and after the therapy. To evaluate the relation between the difference of whole exome sequencing and immunological parameters of patients treated with this regimen. To evaluate the relation between the difference of whole exome sequencing and the prognosis of patients treated with this regimen. Outpatient visit, laboratory findings
Time frame: One month before therapy and one month after therapy
Correlation between circulating tumor DNA (ctDNA) and serum tumor marker before and after neoadjuvant therapy, before and after curative resection, during and after adjuvant therapy, and during and after the maintenance treatment of immunotherapy
To evaluate the correlation between ctDNA and serum tumor markers, such as CA199, CA125, and CEA levels of patients. Outpatient visit, laboratory findings
Time frame: One month during therapy and 3 months thereafter up to 24 months
Correlation between ctDNA and CT evaluations before and after neoadjuvant therapy, before and after curative resection, during and after adjuvant therapy, and during and after the maintenance treatment of immunotherapy
To evaluate the consistency between ctDNA and CT evaluations of patients. Outpatient visit, laboratory findings
Time frame: One month during therapy and 3 months thereafter up to 24 months
Correlation among ctDNA, serum tumor markers, and CT evaluations before and after neoadjuvant therapy, before and after curative resection, during and after adjuvant therapy, and during and after the maintenance treatment of immunotherapy.
To evaluate the correlation among ctDNA, serum tumor markers, and CT evaluations of patients. Outpatient visit, laboratory findings
Time frame: One month during therapy and 3 months thereafter up to 24 months
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