Perioperative Treatment in High-risk Resectable Pancreatic Cancer With NALIRIFOX

NALIRIFOX as Perioperative Treatment in Patients With High-risk Resectable Pancreatic Cancer : a Multicenter, Randomized, Open-label Trial

This multicentric randomized trial will compare the efficacy and safety of neoadjuvant chemotherapy + surgery + adjuvant chemotherapy or surgery + adjuvant chemotherapy in patients with high-risk resectable pancreatic cancer. NALIRIFOX (5-fluorouracil, leucovorin, irinotecan liposome injection and oxaliplatin) will be used as the chemotherapy regimen.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Irinotecan liposome injection; Drug: Oxaliplatin; Drug: 5-FU; Drug: LV

Detailed Description

Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose,improve the efficacy and reduce the toxic side effects. The aim of this study is to compare the efficacy and safety of NALIRIFOX + surgery + NALIRIFOX or surgery + NALIRIFOX in high-risk patients with resectable pancreatic cancer.

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Guo Shiwei, Professor; Phone Number: 18621500666; Email: guoshiwei@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: ≥18 years old.
2. Histologically or cytologically proven pancreatic ductal adenocarcinoma.
3. Multidisciplinary assessment as high-risk resectable disease.
4. At least one measurable lesion (according to RECIST v1.1).
5. No prior antitumor therapy for pancreatic cancer.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 1.
7. The expected survival time ≥3 months.

8. Subject has adequate biological parameters as demonstrated by the following blood counts:

   Absolute neutrophil count (ANC) ≥1.5×10^9/L Platelet count ≥100×10^9/L Hemoglobin (Hgb) ≥90 g/L White blood cell（WBC）≥3.0×10^9/L

9. Adequate hepatic function as evidenced by:

   Serum total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) 、alkaline phosphatase（ALP）and alanine aminotransferase (ALT) ≤2.5 × ULN

10. Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 × ULN or creatinine clearance ≥60 mL/min.
11. Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.

Exclusion Criteria:

1. Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
2. Patients with distant metastases and/or can not complete resection.
3. Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
4. Active HIV, HBV, HCV infection.
5. Combined with uncontrollable systemic diseases (such as unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmia, severe pericardial disease history and other cardiovascular diseases; hypertension > grade 2 after medication [CTCAE v5.0], diabetes, etc.)
6. Presence of severe gastrointestinal disease (including active bleeding, > grade 1 obstruction [CTCAE v5.0], or > grade 1 diarrhea [CTCAE v5.0])
7. History of allergy or hypersensitivity to drug or any of their excipients.
8. Patients who have chemotherapy and surgery contraindications.
9. Documented serum albumin ≤3 g/dL
10. Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
11. Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
12. Participated in other trial within 30 days prior to the first dose of study treatment.
13. Patients who are not suitable to participate in this trial for any reason judged by the investigator

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: Group A: NALIRIFOX + surgery + NALIRIFOX; Patients receive 8 cycles of NALIRIFOX. Then undergo surgery and receive 4 cycles of NALIRIFOX after surgery. NALIRIFOX consists of irinotecan liposome injection, oxaliplatin, 5 FU/LV	Drug: Irinotecan liposome injection; 50 mg/m² on Day 1 of a 14 day cycle; Other Names: Nal-IRI; Drug: Oxaliplatin; 60 mg/m² on Day 1 of a 14 day cycle; Other Names: Eloxatin®; Drug: 5-FU; 2400 mg/m² continuous IV infusion in 46 h; Other Names: 5-Fluorouracil; Adrucil®; flurouracil; Drug: LV; 400 mg/m² on Day 1 of a 14 day cycle; Other Names: Leucovorin; Folinic Acid
Active Comparator: Group B: surgery + NALIRIFOX; Patients receive 12 cycles of NALIRIFOX after surgery. NALIRIFOX consists of irinotecan liposome injection, oxaliplatin, 5 FU/LV.	Drug: Irinotecan liposome injection; 50 mg/m² on Day 1 of a 14 day cycle; Other Names: Nal-IRI; Drug: Oxaliplatin; 60 mg/m² on Day 1 of a 14 day cycle; Other Names: Eloxatin®; Drug: 5-FU; 2400 mg/m² continuous IV infusion in 46 h; Other Names: 5-Fluorouracil; Adrucil®; flurouracil; Drug: LV; 400 mg/m² on Day 1 of a 14 day cycle; Other Names: Leucovorin; Folinic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Overall Survival Rate	Defined as the percentage of patients who are alive at 2 years after randomization (proportion of patients alive will estimated by the survival curve)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1	4 months
Surgical Conversion Rate（R0 / R1 resection）	Defined as the percentage of patients that underwent a R0/R1 resection	5 months
R0 resection rate	Defined as the proportion of patients who have achieved R0 resection	5 months
Event-free Survival	Defined as the time between signing the informed consent form to the first documentation of event where events considered are 1) disease progression (local recurrence, new lesions or distant metastasis), 2) a second malignant tumor occurs, or 3) death due to any cause	1 year
Overall survival	Defined as the time between signing the informed consent form and death due to various causes	2 years
Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading	7 months

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Principal Investigator: Jin Gang, Professor, Changhai hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: perioperative; NALIRIFOX; high-risk resectable
• 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; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan
• Other Study ID Numbers: CSPC-DEY-PC-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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