Monthly Alternating NALIRIFOX and GnP in the First-Line Setting for Metastatic Pancreatic Ductal Adenocarcinoma

A prospective, interventional, single-center, single-arm, open-label, phase II study for patients with metastatic pancreatic cancer. The intervention consists of monthly alternating standard chemotherapy regimens-NALIRIFOX and GnP. The hypothesis is that induction therapy with alternating NALIRIFOX and GnP has better efficacy compared to historical observation.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: NALIRIFOX; Drug: Gemcitabine plus nab-Paclitaxel (GnP)

• Study Type: Interventional
• Enrollment (Estimated): 41
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: GI Trial Referral; Phone Number: 5167348896; Email: gitrialreferral@northwell.edu
• Study Contact Backup: Name: Lalta Dhanantwari, MBA; Phone Number: 5167348896; Email: ldhanantwari@northwell.edu

Study Locations

• United States
  • New York
    • Bay Shore, New York, United States, 11706
      • Recruiting
      • Imbert Cancer Center
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu
    • Mount Kisco, New York, United States, 10549
      • Recruiting
      • Northern Westchester Cancer Center
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu
    • New Hyde Park, New York, United States, 11040
      • Recruiting
      • Long Island Jewish Medical Center
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu
    • New Hyde Park, New York, United States, 11042
      • Recruiting
      • Zuckerberg Cancer Center
      • Contact: Daniel King, MD; Phone Number: 5167348900; Email: dking14@northwell.edu
      • Principal Investigator: Daniel King, MD, PhD
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu
    • New York, New York, United States, 10065
      • Recruiting
      • Manhattan Eye, Ear and Throat Hospital
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu
    • Rego Park, New York, United States, 11374
      • Recruiting
      • NHPP Medical Oncology at Rego Park
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu
    • Sleepy Hollow, New York, United States, 10591
      • Recruiting
      • Phelps Cancer Center
      • Contact: GI Trial Referral; Phone Number: 516-734-8896; Email: gitrialreferral@northwell.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion:

• >18 years of age
• Histologically proven pancreatic ductal adenocarcinoma, poorly differentiated carcinoma, or adenosquamous carcinoma
• Radiographic evidence of metastatic disease
• At least 1 measurable target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Metastatic relapse of previously resected pancreatic cancer is allowed provided the patient is more than 6 months from last SOC adjuvant treatment
• ECOG PS 0-1

• Laboratory assessments within 14 days as indicated below:

  • Hemoglobin > 9.0 g/dL (patients with hemoglobin < 9 g/dL may be transfused prior to study enrollment)
  • Platelet count > 100 x 10^9/L
  • Absolute neutrophil count (ANC) > 1.5 x 10^9/L
  • Total bilirubin < 3 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x ULN (if liver metastases are present, AST and ALT < 5 x ULN is permitted.
  • Creatinine ≤1.5 ULN
  • Creatinine clearance > 40 mL/min as calculated by Cockcroft-Gault formula
  • APTT (aPTT) ≤ 1.5 × ULN. For subjects receiving unfractionated heparin < 2.5 × ULN, or within acceptable range considered by the investigator.
  • PT/INR INR ≤ 1.5 × ULN. For subjects receiving warfarin, 2.0 -3.0, or within acceptable range considered by the investigator.
• Women of childbearing potential must be surgically sterile or postmenopausal or must have a negative pregnancy test (serum or urine) prior to study enrolment and must use effective barrier contraception or abstinence during the treatment period. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions and therefore are not considered effective for this study. Male patients must be surgically sterile or use effective contraception or abstinence during the treatment period. The definition of effective contraception will be based on investigator discretion. Female and male patients are advised to use effective contraceptives for at least 9 months after the last treatment dose.
• Ability to understand and willing to sign informed consent form

Exclusion:

• A history of other disease, metabolic dysfunction, physical examination finding or clinical laboratory test result suspicious of a disease or condition which, in the opinion of the investigator, would compromise patient safety due to risk of treatment complications or could affect interpretation of the study results
• Ampullary, acinar, squamous, and neuroendocrine histology
• Presence of central nervous system metastases
• Life expectancy < 12 weeks
• Pregnant or breastfeeding women
• Prior neuropathy > grade 1 as per CTCAE v5
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Major surgery within 4 weeks prior to initiation of the study treatment, without full recovery
• Any past chemotherapy delivered for metastatic pancreatic cancer
• Known somatic or germline mutations in BRCA1, BRCA2, or PALB2
• Active second malignancy whose prognosis has a high likelihood of impacting survival
• Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results. Patients also unwilling or unable to comply with study procedures and/or study visits, including long-term follow-up for survival.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NALIRIFOX; NALIRIFOX consists of 5-FU 2400 mg/m2 over 46 hours, liposomal irinotecan 50 mg/m2, and oxaliplatin 60 mg/m2, which would be given on Day 1 and Day 15	Drug: NALIRIFOX; NALIRIFOX consists of 5-FU 2400 mg/m2 over 46 hours, liposomal irinotecan 50 mg/m2, and oxaliplatin 60 mg/m2, which would be given on Day 1 and Day 15; Other Names: 5fu/ leucovorin / oxaliplatin / liposomal irinotecan
Active Comparator: Gemcitabine plus nab-Paclitaxel (GnP); GnP consists of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2, given on Days 1, 8, and 15.	Drug: Gemcitabine plus nab-Paclitaxel (GnP); GnP consists of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2, given on Days 1, 8, and 15.; Other Names: Gemcitabine/nab-Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine 6-month Progression Free Survival (PFS)	The primary endpoint is 6-month PFS rate defined as the proportion of patients alive and progression free (by RECIST v.1.1) at 6 months after treatment initiation. PFS events will be classified as either local progression, distant recurrence, secondary malignancy, or death.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall response rate, defined as the proportion of patients whose best response is partial response or complete response by RECIST v.1.1	24 months
Disease Control Rate	Disease control rate, defined as the proportion of patients whose best response is stable disease, partial response, or complete response, by RECIST v.1.1	24 months
Overall Survival	OS, defined as the time from treatment initiation to death. Patients living without disease progression will be censored at the date of last assessment	24 months
Determine Toxicities using the NCI CTCAE v. 5.0	AEs will be monitored, and the incidence, severity, and relationship to study drug will be reported.	24 months
Time to Treatment Failure	Time to treatment failure, defined as the time from treatment initiation to discontinuation of treatment, either due to progression or intolerance	24 months

Collaborators and Investigators

• Sponsor: Northwell Health

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2025
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): June 20, 2027

Study Registration Dates

• First Submitted: July 14, 2025
• First Submitted That Met QC Criteria: September 2, 2025
• First Posted (Actual): September 9, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Gemcitabine; Fluorouracil; Leucovorin; 130-nm albumin-bound paclitaxel; irinotecan sucrosofate
• Other Study ID Numbers: 24-0950

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No