AG Combined With Immunotherapy and SBRT in Patients With Potentially Resectable Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the efficacy and safety of concurrent chemoradiotherapy combined with immunotherapy in patients with potentially resectable pancreatic cancer.

Detailed Description
-----------------
Due to the hidden onset and rapid progression of pancreatic cancer, most patients are already locally advanced or have distant metastasis at the time of diagnosis and lose the opportunity for surgery. Even among operable patients, about 50% will have recurrence and metastasis one year after surgery. Therefore, more and more evidence supports neoadjuvant therapy for patients with high risk factors for resectable pancreatic cancer, and conversion therapy followed by surgery for patients with borderline resectable and locally advanced pancreatic cancer. Therefore, the objective of this study is to evaluate the efficacy and safety of concurrent chemoradiotherapy combined with immunotherapy in patients with potentially resectable pancreatic cancer.

Official Title
-----------------
Efficacy and Safety of AG Combined With Immunotherapy and SBRT in Patients With Potentially Resectable Pancreatic Cancer

Conditions
-----------------
Pancreatic Carcinoma

Intervention / Treatment
-----------------
* Drug: Toripalimab
* Drug: Gemcitabine
* Drug: Nab paclitaxel
* Other: SBRT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >= 18 years； Eastern Cooperative Oncology Group (ECOG) score of 0-1; Pancreatic cancer confirmed by histology or cytology; Potentially resectable pancreatic cancer documented by contrast enhanced CT (or MRI) scan; Hematological indexes: Neutrophil count >= 1.5 x 10^9/L Hemoglobin >= 10g / dl Platelet count >= 100 x 10^9/L; Biochemical indicators: Total bilirubin <= 1.5 x upper limit of normal value (ULN); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 1.5 x ULN; Creatinine clearance rate >= 60ml / min. Participants of childbearing age need to take appropriate protective measures (contraceptive measures or other methods of birth control) before entering the group and during the test; Signed informed consent; Follow the protocol and follow-up procedures. Exclusion Criteria: Have received systematic anti-tumor treatment. Previous history of other tumors, except for cervical cancer in situ, treated squamous cell carcinoma or bladder epithelial tumor (TA and TIS) or other malignant tumors that have received radical treatment (at least 5 years before enrollment). Active bacterial or fungal infection (> = level 2 of National Cancer Institute Common Toxicity Criteria (NCI-CTC), Version 3.0). Human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) infection, uncontrollable coronary artery disease or asthma, uncontrollable cerebrovascular disease or other diseases considered by researchers to be out of the group. Autoimmune diseases or immune defects who are treated with immunosuppressive drugs. Pregnant and lactating women. Pregnant women of childbearing age must be tested negative within 7 days before entering the group. Drug abuse, clinical or psychological or social factors make informed consent or research implementation affected. Allergic to programmed cell death protein-1 (PD-1) monoclonal antibody immunotherapy drugs.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent radiochemotherapy combined with immunotherapy<br>Participants will receive toripalimab plus gemcitabine and nab-paclitaxel in cycles of 21 days. Non-progressors will plus concurrent radiotherapy during the 3rd cycle of chemotherapy. After 4-6 cycles treatment, Multiple disciplinary team (MDT) will evaluate whether to undergo radical surgery. | Drug: Toripalimab<br>* Toripalimab 240mg administered intravenously on Days 1 of every 3 weeks<br>Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m^2 administered intravenously on Days 1 & 8 of every 3 weeks<br>Drug: Nab paclitaxel<br>* Nab paclitaxel 125 mg/m^2 administered intravenously on Days 1 & 8 of every 3 weeks.<br>Other: SBRT<br>* SBRT Radiotherapy plan: Planning gross tumor volume (PGTV) 5Gy*10 fractions, Planning target volume (PTV) 3Gy*10 fractions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | RECIST Version 1.1 RECIST Version 1.1 RECIST Version 1.1 RECIST Version 1.1 RECIST Version 1.1 RECIST Version 1.1 | 2 years | 
| R0 resection rate | R0 resection rate | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| os | OS is defined as the time from randomization to death due to any cause. | 3 years | 
| pfs | PFS is defined as the time from the first day of randomization to the date of first record of disease progression or death. | 3 years | 
| dcr | DCR including CR, PR, and SD | 3 years | 
| Adverse Events | Adverse event (AE)、Serious adverse event (SAE) | 3 years |