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

Pancreatic Cancer Stage III Clinical Trial

Official title:

A Phase II Study to Evaluate the Safety and Efficacy of Sintilimab Combined With Nab-paclitaxel and Gemcitabine for Neoadjuvant and Adjuvant Therapy of Patients With Resectable and Borderline Resectable Pancreatic Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05562297
• Other study ID #: ZSPAC-01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: October 1, 2026

Study information

• Verified date: June 2023
• Source: Shanghai Zhongshan Hospital
• Contact: Wen-Quan Wang, MD, PhD
• Phone: +86 21 31587861
• Email: wang.wenquan[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: October 1, 2026
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Pancreatic Cancer Stage III
• Pancreatic Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Zhongshan Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital	Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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