Clinical trial NCT05562297: 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
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Fudan University
First posted: 2022-09-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 2-year overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
timeFrame: 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 outcomes:
measure: Overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
timeFrame: 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
measure: Event-free survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
timeFrame: 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
measure: Objective response rate and disease control rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: Recurrence-free survival after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: Resection rate and R0 resection rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: Major pathological response rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: 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
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: 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
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: Number and severity of toxicities according to NCI CTCAE version 4.0
timeFrame: One week during therapy and 3 months thereafter up to 24 months
measure: Correlation between patients' immunological parameters before and after the application of sintilimab and gemcitabine plus nab-paclitaxel and prognosis of them
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: Whole exome sequencing before and after the application of sintilimab and gemcitabine plus nab-paclitaxel
timeFrame: One month before therapy and one month after therapy
measure: 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
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: 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
timeFrame: One month during therapy and 3 months thereafter up to 24 months
measure: 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.
timeFrame: One month during therapy and 3 months thereafter up to 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Liang Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Zhongshan Hospital
name: Wen-hui Lou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: