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

Phase 2

Not yet recruiting

• Conditions: Borderline Resectable Pancreatic Ductal Adenocarcinoma
• Interventions: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan Sucrosofate; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Procedure: Surgical Procedure

• Registration Number: NCT06821997
• Lead Sponsor: Roswell Park Cancer Institute

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2025-02-06
• Study First Submitted QC: 2025-02-06
• Study First Posted: 2025-02-12
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-06
• Study Start: 2025-06-01
• Primary Completion: 2027-03-01
• Study Completion: 2027-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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 Cancer Network 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 hematopoietic growth factors
• Platelet count ≥ 100,000 cells/uL
• Hemoglobin ≥ 9 g/dL
• Plasma total bilirubin ≤ upper limit of normal (ULN) (biliary drainage is allowed for 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 Solid Tumors (RECIST) 1.1 criteria
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form (ICF) prior to receiving any study related procedure

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) or dihydropyrimidine dehydrogenase (DPD) polymorphisms (DPYD*2A [rs3918290, c.1905+1G>A, IVS14+1G>A], c.2846A>T [rs67376798, D949V], c.1679T>G [rs55886062, DPYD*13, I560S], and c.1236G>A [rs56038477, E412E, in haplotype B3]) known to significantly impact CPT-11 and fluorouracil metabolism and associated with increased risk for toxicities
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with 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 an unsuitable candidate to receive study drug

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (NALIRIFOX)	Biospecimen Collection	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.
Treatment (NALIRIFOX)	Computed Tomography	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.
Treatment (NALIRIFOX)	Fluorouracil	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.
Treatment (NALIRIFOX)	Irinotecan Sucrosofate	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.
Treatment (NALIRIFOX)	Leucovorin Calcium	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.
Treatment (NALIRIFOX)	Oxaliplatin	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.
Treatment (NALIRIFOX)	Surgical Procedure	Patients receive liposomal irinotecan 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 CT and blood sample collection throughout the study.

Primary Outcome Measures

Name	Time	Method
Major pathologic response (MPR)	Up to 5 years	MPR will be defined as either complete pathologic response or minimal residual cancer based on the American College of Pathology system. The MPR status will be summarized using frequencies and relative frequencies.

Secondary Outcome Measures

Name	Time	Method
Carcinoembryonic antigen response rate	Up to 5 years	Will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method
Objective response rate (ORR)	Up to 5 years	Will be assessed using Response Evaluation Criteria in Solid Tumors 1.1. ORR will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method.
CA19-9 response rate	Up to 5 years	Will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method.
Positive margin resection rate	Up to 5 years	Will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method
Disease-free survival	From start of neoadjuvant therapy until disease progression, subsequent therapy, death due to any cause, or last follow-up, assessed up to 5 years	Will be summarized using standard Kaplan-Meier methods, where estimates of the median times will be obtained with 90% confidence intervals.
Overall survival	From start of neoadjuvant therapy until death due to any cause, or last follow-up, assessed up to 5 years	Will be summarized using standard Kaplan-Meier methods, where estimates of the median times will be obtained with 90% confidence intervals
Incidence of adverse events	Up to 30 days after the last intervention, or until the event has resolved, the study participant is lost to follow-up, the start of a new treatment, or until the study investigator assesses the event(s) as stable or irreversible	Will be described and graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be summarized by attribution and grade using frequencies and relative frequencies.

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States