NALIRIFOX Before Surgery for the Treatment of Borderline Resectable Pancreatic Ductal Adenocarcinoma, Nectar Trial

Phase

Condition

Adenocarcinoma

Treatment

Surgical Procedure

Oxaliplatin

Computed Tomography

Clinical Study ID

NCT06821997

I-4064824

NCI-2025-00732

Ages > 18
All Genders

Study Summary

This phase II trial tests how well liposomal irinotecan, oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) before surgery works in treating patients with pancreatic ductal adenocarcinoma that is close to major blood vessels, but is still potentially removable by surgery (borderline resectable). Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Liposomal irinotecan is a form of the anticancer drug irinotecan that is contained inside very tiny, fat-like particles. Liposomal irinotecan may have fewer side effects and work better than other forms of the drug. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. 5-fluorouracil, a type of antimetabolite, stops cells from making DNA and it may kill tumor cells. Leucovorin, a form of folic acid, is used to lessen the toxic effects of substances that block the action of folic acid. It is a type of chemoprotective agent and a type of chemosensitizing agent. Giving NALIRIFOX before surgery may improve the chance of successful surgery and decrease the chance of the cancer returning after surgery in patients with borderline resectable pancreatic ductal adenocarcinoma.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age ≥ 18 years of age
Have histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) that is borderline resectable (BR) using the National Comprehensive CancerNetwork criteria
Have a documented Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
Absolute neutrophil count (ANC) ≥ 1,500 cells/uL without the use of hematopoieticgrowth factors
Platelet count ≥ 100,000 cells/uL
Hemoglobin ≥ 9 g/dL
Plasma total bilirubin ≤ upper limit of normal (ULN) (biliary drainage is allowedfor biliary obstruction)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
Creatine clearance of > 30 mL/min (per Cockroft-Gault equation)
Plasma albumin ≥ 3 g/dL
Have measurable or evaluable disease per Response Evaluation Criteria in SolidTumors (RECIST) 1.1 criteria
Participants of child-bearing potential must agree to use adequate contraceptivemethods (e.g., hormonal or barrier method of birth control; abstinence) prior tostudy entry. Should a woman become pregnant or suspect she is pregnant while she orher partner is participating in this study, she should inform her treating physicianimmediately
Participant must understand the investigational nature of this study and sign anindependent ethics committee/institutional review board approved written informedconsent form (ICF) prior to receiving any study related procedure

Exclusion

Exclusion Criteria:

Patients who have had previous chemotherapy or radiotherapy for PDAC
Patients with resectable, unresectable, or metastatic PDAC
Presence of germline glucuronosyltransferase (UGT) 1A1 (28 or 6) ordihydropyrimidine dehydrogenase (DPD) polymorphisms (DPYD2A [rs3918290,c.1905+1G>A, IVS14+1G>A], c.2846A>T [rs67376798, D949V], c.1679T>G [rs55886062,DPYD13, I560S], and c.1236G>A [rs56038477, E412E, in haplotype B3]) known tosignificantly impact CPT-11 and fluorouracil metabolism and associated withincreased risk for toxicities
Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements
Pregnant or nursing female participants
Unwilling or unable to follow protocol requirements
Any condition which in the investigator's opinion deems the participant anunsuitable candidate to receive study drug

Study Design

Surgical Procedure

March 02, 2026

March 01, 2027

Study Description

PRIMARY OBJECTIVE:

I. To determine the antitumor efficacy of the combination of irinotecan sucrosofate (liposomal irinotecan), oxaliplatin and infusional fluorouracil (5-fluorouracil)/leucovorin calcium (leucovorin) (NALIRIFOX) in patients with borderline resectable pancreatic ductal adenocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate clinical efficacy and tolerability of the proposed treatment regimen.

II. To determine the safety of liposomal irinotecan, oxaliplatin and infusional fluorouracil in patients with borderline resectable pancreatic ductal adenocarcinoma.

EXPLORATORY OBJECTIVES:

I. To evaluate blood-based biomarkers predictive of short- and long-term outcomes.

II. To generate tumor tissue-based biomarkers predictive of short- and long-term outcomes.

OUTLINE:

Patients receive liposomal irinotecan intravenously (IV) over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin IV over 30 minutes and fluorouracil IV over 48 hours on day 1 of each cycle. Cycles repeat every 14 days for 4-8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo surgical resection 4-8 weeks after the last treatment dose. Starting 4-12 weeks after surgery, patients receive liposomal irinotecan, oxaliplatin, leucovorin, and fluorouracil for up to 4 additional cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up within 30 days, every 3-6 months for 2 years, then every 6-12 months for up to 5 years.

Connect with a study center

Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Active - Recruiting
Roswell Park Cancer Institute
Buffalo 5110629, New York 5128638 14263
United States
Site Not Available

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