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

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

This is a prospective, single-center, randomized, controlled phase Ⅲ study.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Pancreatic Adenocarcinoma; Borderline Resectable Pancreatic Cancer
• Intervention / Treatment: Drug: Nab paclitaxel plus gemcitabine; Drug: mFOLFIRINOX

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xian-Jun Yu, MD, PhD; Phone Number: +86 21 64175590; Email: yuxianjun@fudanpci.org
• Study Contact Backup: Name: Wen-Quan Wang, MD, PhD; Phone Number: +86 21 64175590; Email: wangwenquan@fudanpci.org

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: albumin bound 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.	Drug: Nab paclitaxel plus gemcitabine; 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.; Other Names: AG regimen
Active Comparator: mFOFLIRINOX; 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; 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.; 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

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 2, 2020
• First Posted (Actual): November 5, 2020

Study Record Updates

• Last Update Posted (Actual): January 28, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; mFOLFIRINOX; albumin bound paclitaxel
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel; Folfirinox
• Other Study ID Numbers: CSPAC-28

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No