Neoadjuvant/Adjuvant Sintilimab, Nab-paclitaxel, And Gemcitabine For Resectable/Borderline Resectable Pancreatic Cancer

Study Overview

Neoadjuvant/Adjuvant Sintilimab, Nab-paclitaxel, and Gemcitabine for Resectable/Borderline Resectable Pancreatic Cancer

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.

Pancreatic Cancer, Stage IB
Pancreatic Cancer, Stage IIA
Pancreatic Cancer, Stage IIB
Pancreatic Cancer Stage III

DRUG: sintilimab
DRUG: nab-paclitaxel
DRUG: gemcitabine

ZSPAC-01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-09-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-19
First Submitted that Met QC Criteria 2022-09-27	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-22
First Posted (ACTUAL) 2022-09-30	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: sintilimab + nab-paclitaxel + gemcitabine Experimental: sintilimab + nab-paclitaxel + gemcitabine nab-paclitaxel at 125 mg/m^2 on days 1, and 8; gemcitabine at 1000 mg/m^2 on days 1, and 8; sintilimab at 200mg on day 1;	DRUG: sintilimab 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. DRUG: nab-paclitaxel 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. DRUG: gemcitabine 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: sintilimab + nab-paclitaxel + gemcitabine

Experimental: sintilimab + nab-paclitaxel + gemcitabine nab-paclitaxel at 125 mg/m^2 on days 1, and 8; gemcitabine at 1000 mg/m^2 on days 1, and 8; sintilimab at 200mg on day 1;

DRUG: sintilimab

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.

DRUG: nab-paclitaxel

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.

DRUG: gemcitabine

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.

Primary Outcome Measures	Measure Description	Time Frame
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	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

Secondary Outcome Measures	Measure Description	Time Frame
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	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	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	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	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	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	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	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	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	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	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	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	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	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	One month during therapy and 3 months thereafter up to 24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Wen-Quan Wang, MD, PhD

Phone Number: +86 21 31587861

Email: wang.wenquan@zs-hospital.sh.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Signed informed content obtained prior to treatment
Age ≥ 18 years and ≤ 75 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Patients must have imaging evaluations to confirm that their pancreatic adenocarcinoma is resectable and borderline resectable. Patients must have histologically confirmed pancreatic adenocarcinoma, too.
Therapy-naïve for their pancreatic cancer. Patients should receive no anti-tumor treatment, including systemic chemotherapy, interventional chemotherapy, high-energy focused ultrasound, radiotherapy, immunotherapy, molecular targeted therapy, and anti-tumor Chinese medicine therapy.
No serious dysfunction in blood system, heart, lung function, or autoimmune system (refer to the respective diagnostic criteria)
White blood cell (WBC) ≥ 3 × 109/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelets (PLT) ≥ 100 × 109/L; Hemoglobin (Hgb) ≥ 90 g/L
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin (TBIL) ≤ ULN; Creatinine (CRE) ≤ 1.5 × ULN
Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN
Able to comply with research visit plans and other protocol requirements.

The diameter of the resectable tumor is ≤ 2 cm in imaging evaluation
Associated with other malignant tumors
Patients receiving anti-tumor treatment before neoadjuvant therapy, including systemic chemotherapy, interventional chemotherapy, high-energy focused ultrasound, radiotherapy, immunotherapy, molecular targeted therapy, and anti-tumor Chinese medicine therapy
Use of any other investigational agents
Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or nursing women
History of allergic reactions attributed to compounds of similar chemical or biological composition to nab-paclitaxel, gemcitabine, or sintilimab
Patients who are using and need to use warfarin for a long period
Patients who are unwilling or unable to comply with study procedures
Patients who are expected to be out of the observation period for 14 days or more during the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Fudan University

Investigators

PRINCIPAL_INVESTIGATOR: Liang Liu, MD, PhD, Shanghai Zhongshan Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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