Perioperative Treatment in High-risk Resectable Pancreatic Cancer With NALIRIFOX

Phase 2

Not yet recruiting

• Conditions: Pancreatic Cancer
• Interventions: Drug: Irinotecan liposome injection; Drug: Oxaliplatin; Drug: 5-FU; Drug: LV

• Registration Number: NCT06210360
• Lead Sponsor: Changhai Hospital

Brief Summary

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.

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 Timeline

• Status Verified: 2023-12
• Study First Submitted: 2024-01-02
• Study First Submitted QC: 2024-01-17
• Last Update Submitted: 2024-01-17
• Study First Posted: 2024-01-18
• Last Update Posted: 2024-01-18
• Study Start: 2024-02-01
• Primary Completion: 2025-04-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 134

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: NALIRIFOX + surgery + NALIRIFOX	Irinotecan liposome injection	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
Group A: NALIRIFOX + surgery + NALIRIFOX	Oxaliplatin	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
Group A: NALIRIFOX + surgery + NALIRIFOX	LV	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
Group B: surgery + NALIRIFOX	LV	Patients receive 12 cycles of NALIRIFOX after surgery. NALIRIFOX consists of irinotecan liposome injection, oxaliplatin, 5 FU/LV.
Group A: NALIRIFOX + surgery + NALIRIFOX	5-FU	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
Group B: surgery + NALIRIFOX	Irinotecan liposome injection	Patients receive 12 cycles of NALIRIFOX after surgery. NALIRIFOX consists of irinotecan liposome injection, oxaliplatin, 5 FU/LV.
Group B: surgery + NALIRIFOX	Oxaliplatin	Patients receive 12 cycles of NALIRIFOX after surgery. NALIRIFOX consists of irinotecan liposome injection, oxaliplatin, 5 FU/LV.
Group B: surgery + NALIRIFOX	5-FU	Patients receive 12 cycles of NALIRIFOX after surgery. NALIRIFOX consists of irinotecan liposome injection, oxaliplatin, 5 FU/LV.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	4 months	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1
Surgical Conversion Rate（R0 / R1 resection）	5 months	Defined as the percentage of patients that underwent a R0/R1 resection
R0 resection rate	5 months	Defined as the proportion of patients who have achieved R0 resection
Event-free Survival	1 year	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
Overall survival	2 years	Defined as the time between signing the informed consent form and death due to various causes
Incidence of adverse events	7 months	Use NCI-CTCAE version 5.0 for classification and grading