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

NCT06821997 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: I-4064824NCI-2025-00732
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Borderline Resectable Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Objective response rate (ORR)

  Up to 5 years

• CA19-9 response rate

  Up to 5 years

• Carcinoembryonic antigen response rate

  Up to 5 years

• Positive margin resection rate

  Up to 5 years

• 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

Study Arms (1)

Treatment (NALIRIFOX)

EXPERIMENTAL

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: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Irinotecan Sucrosofate; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Procedure: Surgical Procedure

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (NALIRIFOX)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (NALIRIFOX)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (NALIRIFOX)

Irinotecan Sucrosofate DRUG

Given IV

Also known as: inotecan Hydrochloride as Sucrosulfate Salt Form Liposomal Formulation, Irinotecan Liposome, Irinotecan Sucrosofate Liposome, Irinotecan Sucrosofate-containing Pegylated Liposomal Formulation, MM 398, MM-398, MM398, nal-IRI, Nanoliposomal Irinotecan, Nanoliposomal Irinotecan as Sucrosofate, Nanoparticle Liposome Formulation of Irinotecan, Onivyde, PEP 02, PEP-02, PEP02

Treatment (NALIRIFOX)

Leucovorin Calcium DRUG

Given IV

Also known as: 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, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (NALIRIFOX)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, Elplat, JM 83, JM-83, JM83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, RP54780, SR 96669, SR-96669, SR96669

Treatment (NALIRIFOX)

Surgical Procedure PROCEDURE

Undergo surgical resection

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (NALIRIFOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Fluorouracil; dehydroftorafur; irinotecan sucrosofate; Leucovorin; Oxaliplatin; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Christos Fountzilas

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 12, 2025
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)