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

NCT ID: NCT06821997

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-01

Study Completion Date

2027-03-01

Brief Summary

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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

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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.

Conditions

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Borderline Resectable Pancreatic Ductal Adenocarcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Fluorouracil

Intervention Type DRUG

Given IV

Irinotecan Sucrosofate

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IV

Oxaliplatin

Intervention Type DRUG

Given IV

Surgical Procedure

Intervention Type PROCEDURE

Undergo surgical resection

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Fluorouracil

Given IV

Intervention Type DRUG

Irinotecan Sucrosofate

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IV

Intervention Type DRUG

Oxaliplatin

Given IV

Intervention Type DRUG

Surgical Procedure

Undergo surgical resection

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography 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 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 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 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 Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christos Fountzilas

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

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Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Ask RPCI

Role: primary

Other Identifiers

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NCI-2025-00732

Identifier Type: REGISTRY

Identifier Source: secondary_id

I-4064824

Identifier Type: OTHER

Identifier Source: secondary_id

I-4064824

Identifier Type: -

Identifier Source: org_study_id