AG vs mFOLFIRINOX as Neoadjuvant Therapy for Borderline Reseactable and Locally Advanced Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
This is a prospective, single-center, randomized, controlled phase Ⅲ study.

Detailed Description
-----------------
Three hundred patients with borderline resectable and locally advanced pancreatic cancer will be randomized 1:1 (150 :150) to the AG and mFOLFIRINOX chemotherapy groups and to observe the overall survival. The AG regimen: albumin-bound paclitaxel and gemcitabine are given intravenous infusion, repeated every 4 weeks for 1, 8, and 15 days, for a total of 4 to 6 cycles. MFOLFIRINOX: Intravenous oxaliplatin for 2 hours, day 1;Intravenous infusion of calcium formyl tetrahydrofolate (LV) for 2 h, day 1;Irinotecan intravenous infusion is added 30 minutes later for 90 minutes, day 1;Intravenous infusion of 5-fluorouracil (5-FU) continued for 46 hours.Repeat every 2 weeks for a total of 4-6 cycles. After neoadjuvant chemotherapy, the surgery will be evaluated according to the patient's tumor and systemic condition. The first cycle of adjuvant chemotherapy begins 4-8 weeks after radical resection, and the choice of adjuvant chemotherapy regimen depends on the response to neoadjuvant chemotherapy.If neoadjuvant chemotherapy is effective, adjuvant chemotherapy maintains the original regimen.Adjuvant chemotherapy has 4 cycles of treatment. Relevant examinations were performed before and after each cycle of medication to assess safety events, imaging review was performed every 2 cycles during the treatment period and every 3 months during the follow-up period.

Official Title
-----------------
A Phase Ⅲ, Randomized Controlled Study to Evaluate the Efficacy and Safety of the Combination of Nab-paclitaxel and Gemcitabine Versus mFOLFIRINOX in Treating Patients With Borderline Reseactable and Locally Advanced Pancreatic Cancer

Conditions
-----------------
Borderline Resectable Pancreatic Cancer, Locally Advanced Pancreatic Adenocarcinoma

Intervention / Treatment
-----------------
* Drug: Nab paclitaxel plus gemcitabine
* Drug: mFOLFIRINOX


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed content obtained prior to treatment Age ≥18 years and ≤ 80 years Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Radiographically confirmed after borderline resectable or locally advanced pancreatic adenocarcinoma. No any other anti-tumor therapy prior to neoadjuvant chemotherapy, including intervention chemoembolization, ablation, radiotherapy, chemotherapy and molecular targeted therapy. No any other anti-tumor therapy prior to neoadjuvant chemotherapy, including intervention chemoembolization, ablation, radiotherapy, chemotherapy and molecular targeted therapy. No serious blood system, heart, lung function abnormalities and immune defects (refer to the respective standards) White blood cell (WBC) ≥ 3 × 109/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelets (PLT) ≥ 100 × 109/L; Hemoglobin (Hgb)≥ 9 g/dL 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 Comply with research visit plans and other program requirements. Exclusion Criteria: with other systemic malignancies Patients who were treated with any other anti-tumor therapy prior to neoadjuvant chemotherapy, including intervention chemoembolization, ablation, radiotherapy, chemotherapy and molecular targeted therapy. used any other study drug within 7 days prior to enrollment; Patients with central nervous system diseases, mental illness, unstable angina pectoris, congestive heart failure, severe arrhythmia and other serious diseases that cannot be controlled History of allergic reactions attributed to compounds of similar chemical or biological composition to study drug and alike. Patients who are using and expected to use warfarin in long term Patients may leave the observation for 14 days or more during the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Three hundred patients with borderline resectable and locally advanced pancreatic cancer are randomized 1:1 to the AG and mFOLFIRINOX chemotherapy groups and to observe the total survival.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: albumin bound paclitaxel plus gemcitabine<br>Albumin-bound paclitaxel and gemcitabine were given intravenous infusion, repeated every 4 weeks for 1, 8, and 15 days, for a total of 4 to 6 cycles. | Drug: Nab paclitaxel plus gemcitabine<br>* Albumin-bound paclitaxel and gemcitabine are given intravenous infusion, repeated every 4 weeks for 1, 8, and 15 days, for a total of 4 to 6 cycle.<br>* Other names: AG regimen;|
| Active Comparator: mFOFLIRINOX<br>Intravenous oxaliplatin for 2 hours, day 1;Intravenous infusion of calcium formyl tetrahydrofolate (LV) for 2 h, day 1;Irinotecan intravenous infusion is added 30 minutes later for 90 minutes, day 1;Intravenous infusion of 5-fluorouracil (5-FU) continued for 46 hours.Repeat every 2 weeks for a total of 4-6 cycles. | Drug: mFOLFIRINOX<br>* Intravenous oxaliplatin for 2 hours, day 1;Intravenous infusion of calcium formyl tetrahydrofolate (LV) for 2 h, day 1;Irinotecan intravenous infusion is added 30 minutes later for 90 minutes, day 1;Intravenous infusion of 5-fluorouracil (5-FU) continued for 46 hours.Repeat every 2 weeks for a total of 4-6 cycles.<br>* Other names: modified FOLFIRINOX regimen;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | To evaluate the overall survival of patients with borderline resectable and locally advanced pancreatic cancer after treated neoadjuvant chemotherapy | from randomization to death, up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence free survival | To evaluate the recurrence free survival of patients with borderline resectable and locally advanced pancreatic cancer after treated neoadjuvant chemotherapy | from randomization to recurrence, up to 36 months | 
| objective response rate | To evaluate the objective response rate of patients with borderline resectable and locally advanced pancreatic cancer after treated neoadjuvant chemotherapy | up to 36 months | 
| resection rate | The proportion of patients who become operable from inoperable after neoadjuvant chemotherapy. | up to 36 months | 
| R0 resection | The proportion of R0 resection among patients who undergo operations. | up to 36 months | 
| postoperative complications | The incidence of postoperative complications | up to 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neoadjuvant chemotherapy, albumin bound paclitaxel, mFOLFIRINOX