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

A Phase 2 Clinical Trial of Nalirifox as Neoadjuvant Treatment for Patients With Borderline Resectable Pancreatic Ductal Adenocarcinoma (Nectar Study)

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.

Study Overview

• Status: Recruiting
• Conditions: Borderline Resectable Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Procedure: Computed Tomography; Procedure: Biospecimen Collection; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Procedure: Surgical Procedure; Drug: Irinotecan Sucrosofate

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Contact: ask rpci; Phone Number: 877-275-7724; Email: askrpci@roswellpark.org
      • Principal Investigator: Christos Fountzilas

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (NALIRIFOX); 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.

Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; SR96669; Elplat; JM 83; JM83; RP54780; SR 96669; Drug: Leucovorin Calcium; Given IV; Other Names: Wellcovorin; folinic acid; Adinepar; Calcifolin; Calcium (6S)-Folinate; Calcium Folinate; Calcium Leucovorin; Calfolex; Calinat; Cehafolin; Citofolin; Citrec; Citrovorum Factor; Cromatonbic Folinico; Dalisol; Disintox; Divical; Ecofol; Emovis; Factor, Citrovorum; Flynoken A; Folaren; Folaxin; FOLI-cell; Foliben; Folidan; Folidar; Folinac; Folinate Calcium; Folinic Acid Calcium Salt Pentahydrate; Folinoral; Folinvit; Foliplus; Folix; Imo; Lederfolat; Lederfolin; Leucosar; leucovorin; Rescufolin; Rescuvolin; Tonofolin; Procedure: Surgical Procedure; Undergo surgical resection; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS; Drug: Irinotecan Sucrosofate; Given IV; Other Names: Onivyde; MM-398; PEP02; Irinotecan Liposome; nal-IRI; Nanoliposomal Irinotecan; Nanoparticle Liposome Formulation of Irinotecan; MM 398; MM398; PEP-02; inotecan Hydrochloride as Sucrosulfate Salt Form Liposomal Formulation; Irinotecan Sucrosofate Liposome; Irinotecan Sucrosofate-containing Pegylated Liposomal Formulation; Nanoliposomal Irinotecan as Sucrosofate; PEP 02

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR)	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.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	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.	Up to 5 years
CA19-9 response rate	Will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method.	Up to 5 years
Carcinoembryonic antigen response rate	Will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method	Up to 5 years
Positive margin resection rate	Will be summarized using frequencies and relative frequencies. Estimates of rates will be obtained with 90% credible regions obtained by Jeffrey's prior method	Up to 5 years
Disease-free survival	Will be summarized using standard Kaplan-Meier methods, where estimates of the median times will be obtained with 90% confidence intervals.	From start of neoadjuvant therapy until disease progression, subsequent therapy, death due to any cause, or last follow-up, assessed up to 5 years
Overall survival	Will be summarized using standard Kaplan-Meier methods, where estimates of the median times will be obtained with 90% confidence intervals	From start of neoadjuvant therapy until death due to any cause, or last follow-up, assessed up to 5 years
Incidence of adverse events	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.	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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Christos Fountzilas, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): February 12, 2025

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin; Specimen Handling; Surgical Procedures, Operative; dehydroftorafur; irinotecan sucrosofate
• Other Study ID Numbers: I-4064824 (Other Identifier: Roswell Park Cancer Institute); NCI-2025-00732 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes