Combination of Anti-PD-1 Antibody and Chemotherapy in Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
The prognosis of pancreatic cancer is extremely poor. NCCN guidelines recommend FOLFIRINOX or modified-FOLFIRINOX as the first-line chemotherapeutic regimen. Studies have shown that immunotherapy with Anti-PD-1 antibody can effectively increase the response rate and prolong patient survival in a number of cancer diseases. Here investigators intend to compare the therapeutic effects of modified-FOLFIRINOX alone and the combination of modified-FOLFIRINOX and Anti-PD-1 antibody in patients with metastatic pancreatic cancer.

Detailed Description
-----------------
Metastatic pancreatic cancer patients will be enrolled in this trial. Investigators will assign patients to the treatment after randomization. The primary endpoint is overall survival. Response rate, progression-free survival, drugs related side effects and other endpoints events will be recorded and analyzed, to assess the combination treatment with modified-FOLFIRINOX and Anti-PD-1 antibody could or couldn't benefit the patients with metastatic pancreatic cancer.

Official Title
-----------------
Comparison of Therapeutic Effect Between Combination of Anti-PD-1 Antibody With mFOLFIRINOX and mFOLFIRINOX Alone in Metastatic Pancreatic Cancer Patients: A Randomized Clinical Trial

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Combination drug
* Drug: Chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: •Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC). Recurrent disease or metastatic disease (such as liver, peritoneum, lung) evaluated by abdominal contrast-enhanced CT, MRI, and chest CT. PET/CT or other imaging examinations would be used if necessary. Never receive any systematic treatment or Progression after fisrt line Gemcitabine base chemotherapy ECOG score 0 or 1. Serum creatinine level is normal, and serum total bilirubin level is less than 1.5 x ULN. ALT and AST are less than 2 x ULN. Signed informed consent. Exclusion Criteria: •History of participation of other clinical trails within 4 weeks History of autoimmune disease or other condition receiving glucocorticoid treatment History of receiving chemotherapy within 2 weeks History of radiotherapy and molecular target therapy within 2 weeks History if active tuberculosis History of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma Major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment. Hematological precancerous diseases, such as myelodysplastic syndromes. Evidence of clinical-related or previous interstitial lung disease, such as noninfectious pneumonia or pulmonary fibrosis, or baseline chest CT scan or chest X-ray findings Previous or physical findings of central nervous system disease, except for adequately treated (e.g. primary brain tumors, uncontrolled seizures or strokes with standard medications) Preexisting neuropathy > 1 (NCI CTCAE). Immune deficiency syndrome, such as active tuberculosis and HIV infection. Allograft requires immunosuppressive therapy or other major immunosuppressive therapies. Severe serious wounds, ulcers or fractures. Clinical evaluation is unacceptable

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemotherapy group<br>Treatment with modified-FOLFIRINOX Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2 | Drug: Chemotherapy<br>* modified-FOLFIRINOX<br>|
| Experimental: Combination group<br>Treatment with modified-FOLFIRINOX and Anti-PD-1 antibody Folic acid 400mg/m^2, 5- fluorouracil 2400mg/m^2 for 46h, irinotecan 135mg/m^2 and oxaliplatin 68mg/m^2, Anti-PD-1 antibody 200mg. | Drug: Combination drug<br>* Accompanying with modified-FOLFIRINOX, Anti-PD-1 antibody was applied biweekly<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The period from the first study treatment to any cause of death | Through the study peirod, for 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resection rate | The number of cases received surgery / the total number of evaluable cases (%) | Through the study peirod, for 3 years | 
| Objective response rate | The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%) | Through the study peirod, for 3 years | 
| Disease control rate | The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%) | Through the study peirod, for 3 years | 
| Progression-free survival | The period from the first treatment to the first evaluation of PD or any cause of death | Through the study peirod, for 3 years | 
| Adverse effects | Adverse events occurring through the study treatment, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc. | Through the study peirod, for 3 years | 
| Carbohydrate antigen 19-9 | The change of CA 199 | Through the study peirod, for 3 years | 
| EORTC QLQ - PAN26 score | The change of the quality of life | Through the study peirod, for 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pancreatic Cancer, Anti-PD-1 Antibody