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

Primary Purpose

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

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

sintilimab

nab-paclitaxel

gemcitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer, Stage IB focused on measuring Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, Sintilimab, Nab-paclitaxel, Gemcitabine, Neoadjuvant Therapy, Adjuvant Therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Zhongshan Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sintilimab + nab-paclitaxel + gemcitabine

Arm Description

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;

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Full Information

NCT ID

NCT05562297

First Posted

September 20, 2022

Last Updated

June 25, 2023

Sponsor

Shanghai Zhongshan Hospital

Collaborators

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT05562297

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

July 1, 2023 (Anticipated)

Primary Completion Date

October 1, 2025 (Anticipated)

Study Completion Date

October 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Zhongshan Hospital

Collaborators

Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, Sintilimab, Nab-paclitaxel, Gemcitabine, Neoadjuvant Therapy, Adjuvant Therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

sintilimab + nab-paclitaxel + gemcitabine

Arm Type

Experimental

Arm Description

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;

Intervention Type

Drug

Intervention Name(s)

sintilimab

Other Intervention Name(s)

Tyvyt

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

nab-paclitaxel

Other Intervention Name(s)

Abraxane

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

gemcitabine

Other Intervention Name(s)

GEMZAR

Intervention Description

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 Measure Information:

Title

2-year overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel

Description

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

Secondary Outcome Measure Information:

Title

Overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel

Description

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

Title

Event-free survival after the application of sintilimab and gemcitabine plus nab-paclitaxel

Description

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

Title

Objective response rate and disease control rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel

Description

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

Title

Recurrence-free survival after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection

Description

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

Title

Resection rate and R0 resection rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection

Description

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

Title

Major pathological response rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection

Description

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

Title

Description

Time Frame

One month during therapy and 3 months thereafter up to 24 months

Title

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

Description

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

Title

Number and severity of toxicities according to NCI CTCAE version 4.0

Description

Time Frame

One week during therapy and 3 months thereafter up to 24 months

Title

Correlation between patients' immunological parameters before and after the application of sintilimab and gemcitabine plus nab-paclitaxel and prognosis of them

Description

Time Frame

One month during therapy and 3 months thereafter up to 24 months

Title

Whole exome sequencing before and after the application of sintilimab and gemcitabine plus nab-paclitaxel

Description

Time Frame

One month before therapy and one month after therapy

Title

Description

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

Title

Description

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

Title

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wen-Quan Wang, MD, PhD

Phone

+86 21 31587861

wang.wenquan@zs-hospital.sh.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Liang Liu, MD, PhD

Organizational Affiliation

Shanghai Zhongshan Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Wen-hui Lou, MD, PhD

Organizational Affiliation

Shanghai Zhongshan Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Zhongshan Hospital

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200000

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wen-Quan Wang, MD, PhD

Phone

+86 21 31587861

wang.wenquan@zs-hospital.sh.cn

First Name & Middle Initial & Last Name & Degree

Liang Liu, MD, PhD

First Name & Middle Initial & Last Name & Degree

Wen-hui Lou, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

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

Learn more about this trial

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

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