Tislelizumab Combined With Nab-paclitaxel and Gemcitabine for Recurrent Pancreatic Cancer

Study Overview
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Brief Summary
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To evaluate the efficacy of Tislelizumab combined with Nab-paclitaxel and Gemcitabine in the treatment of recurrent pancreatic cancer

Detailed Description
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There is heterogeneity in desmoplasia between different metastatic sites in pancreatic cancer. The tumor quasi-characteristics of patients with metastatic PDAC at presentation were more obvious than those of epithelial characteristics, and the quasi-and epithelial subtypes showed different responses to chemotherapy regimens, and the epithelial phenotype tumor quasi-phenotype was associated with metastasis-free survival. Therefore, different metastases of pancreatic cancer may respond differently to medical treatment. There were different metastases after postoperative recurrence of pancreatic cancer, 25.2% had only liver metastases, 14.7% had only lung metastases, 14.7% had multiple distant metastases, and about more than half of the patients had postoperative recurrence with only distant metastases and no in situ metastasis. Then whether there is a difference in the efficacy of PD1 drug therapy in patients with different metastases needs to be further verified.

Official Title
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Prospective Exploratory Study of Tislelizumab Combined With Nab-paclitaxel and Gemcitabine for Postoperative Recurrence of Pancreatic Cancer

Conditions
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Recurrent Pancreatic Cancer

Intervention / Treatment
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* Drug: Tislelizumab
* Drug: Nab paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with radiologically or histologically confirmed postoperative Recurrent Pancreatic Cancer Patients with at least one measurable lesion (according to RECIST 1.1 criteria); Have not received gemcitabine-based regimen after surgery No systemic treatment after diagnosis of recurrence ECOG score 0-1 Expected survival ≥ 3 months; Liver function is essentially normal: absolute neutrophil count > 1500/mm ³; platelet count > 100,000/mm ³; creatinine less than 1.5 times the upper limit of normal or calculated creatinine clearance (CRCI) > 45 mL/min; total bilirubin ≤ 2.0 mg/dL; aspartate aminotransferase (AST) and alanine aminotransferase less than 2.5 times the upper limit of normal Appropriate to participate in this trial as assessed by the investigator before entering the study Male and female subjects of childbearing potential must agree to use an effective method of contraception throughout the study Signed Informed Consent Form Exclusion Criteria: Patients who only undergo abdominal laparotomy but do not undergo resection of pancreatic tumor tissue Received gemcitabine-based regimen after surgery Systemic treatment after diagnosis of recurrence Patients with previous allergic reactions to similar drugs Pregnant or lactating patients Presence of pericardial effusion, uncontrolled pleural effusion, or clinically significant ascites at screening (including detectable ascites or ascites requiring puncture and aspiration on physical examination at screening) History of interstitial lung disease, pneumonitis, or uncontrolled systemic disease, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc Patients with severe cardiovascular diseases within 12 months before enrollment, such as symptomatic coronary heart disease, ≥ grade II congestive heart failure, uncontrolled arrhythmia, myocardial infarction, etc Presence of any active immunodeficiency or autoimmune disease and/or history of any immunodeficiency or autoimmune disease that may recur at screening (e.g., hypothyroidism or hyperthyroidism, interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, etc) Use of steroids or other systemic immunosuppressive therapy 14 days prior to enrollment Patients with other previous malignancies who are not cured Immunodeficient patients, such as HIV-positive Uncontrollable psychosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tislelizumab combined with Nab-paclitaxel and Gemcitabine<br> | Drug: Tislelizumab<br>* Tislelizumab 200 mg every three weeks<br>Drug: Nab paclitaxel<br>* Nab-paclitaxel 125mg/m2 on d1 and d8 every three weeks<br>Drug: Gemcitabine<br>* Gemcitabine 1000mg/m2 on d1 and d8 every three weeks<br>|
| Active Comparator: Nab-paclitaxel and Gemcitabine<br> | Drug: Nab paclitaxel<br>* Nab-paclitaxel 125mg/m2 on d1 and d8 every three weeks<br>Drug: Gemcitabine<br>* Gemcitabine 1000mg/m2 on d1 and d8 every three weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-Year Survival Rates | The proportion of patients who survive more than 1 year after treatment. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate（ORR) | the proportion of patients who had a best overall tumor response rating of complete response (CR) or partial response (PR) | Up to 2 years | 
| Progression Free Survival (PFS) | The time from the date of treatment to the first of either disease progression, relapse or death | Up to 2 years | 
| Overall survival (OS) | The time from the date of treatment start to the date of death or to the date of last follow-up for patients alive | Up to 2 years | 
| Adverse Events (AEs) | the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0; Surgical safety including Intraoperative blood loss，PHLF assessed by ISGLS（2012），Postoperative complications evaluated by modified Clavien-Dindo system. | Up to 2 years |