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

January 19, 2025 updated by: Shanghai Zhongshan Hospital

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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

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

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200000
        • Zhongshan Hospital
        • Contact:
        • Contact:
          • Liang Liu, MD, PhD
        • Contact:
          • Wen-hui Lou, MD, PhD

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.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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.
Other Names:
  • Tyvyt
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.
Other Names:
  • Abraxane
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.
Other Names:
  • GEMZAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-year overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
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
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

Outcome Measure
Measure Description
Time Frame
Overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
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
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
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
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One week during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month before therapy and one month after therapy
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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.
Time Frame: One month during therapy and 3 months thereafter up to 24 months
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

Collaborators and Investigators

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

Sponsor

Shanghai Zhongshan Hospital

Collaborators

Fudan University

Investigators

  • Principal Investigator: Liang Liu, MD, PhD, Shanghai Zhongshan Hospital
  • Principal Investigator: Wen-hui Lou, MD, PhD, Shanghai Zhongshan Hospital

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 Major Dates

Study Start (Estimated)

March 20, 2025

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

September 20, 2022

First Submitted That Met QC Criteria

September 27, 2022

First Posted (Actual)

September 30, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 19, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZSPAC-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The IPD will not be shared with other researchers in order to protect patients' privacy.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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