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

Phase 3

Recruiting

Conditions: Borderline Resectable Pancreatic Cancer
Locally Advanced Pancreatic Adenocarcinoma

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
mFOFLIRINOX	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.
albumin bound paclitaxel plus gemcitabine	Nab paclitaxel plus gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
overall survival	from randomization to death, up to 36 months	To evaluate the overall survival of patients with borderline resectable and locally advanced pancreatic cancer after treated neoadjuvant chemotherapy

Secondary Outcome Measures

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

Locations (1): Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
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Shanghai, Shanghai, China