Monthly alternating NALIRIFOX and gemcitabine plus nab‑paclitaxel for metastatic pancreatic cancer

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

This trial will test whether giving NALIRIFOX and gemcitabine plus nab‑paclitaxel in monthly alternating cycles helps adults with metastatic pancreatic ductal adenocarcinoma control their cancer and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Northwell Health (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 7 sites (Bay Shore, New York and 6 other locations)
• Trial ID: NCT07163273 on ClinicalTrials.gov

What this trial studies

This is a prospective, interventional, single‑arm, open‑label phase II trial conducted at Northwell Health sites enrolling adults with metastatic pancreatic ductal adenocarcinoma. Participants receive monthly alternating cycles of NALIRIFOX and gemcitabine plus nab‑paclitaxel as first‑line systemic therapy, with tumor response tracked by RECIST 1.1 and routine laboratory and imaging assessments. Key eligibility includes at least one measurable metastatic lesion, ECOG performance status 0–1, and adequate blood counts and organ function; prior adjuvant therapy is allowed if completed more than six months before enrollment. The study tests whether this alternating induction approach produces better efficacy compared with historical outcomes from standard regimens.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with histologically confirmed metastatic pancreatic ductal adenocarcinoma, at least one measurable lesion, ECOG 0–1, and adequate blood counts and organ function.

Not a fit: Patients with poor performance status (ECOG ≥2), significant liver or kidney dysfunction, uncontrolled comorbidities, or those who completed adjuvant therapy within six months are unlikely to qualify or derive benefit.

Why it matters

Potential benefit: If successful, the alternating regimen could improve tumor control and survival compared with historical results and offer another first‑line option for patients with metastatic pancreatic cancer.

How similar studies have performed: Standard regimens such as FOLFIRINOX/NALIRIFOX and gemcitabine plus nab‑paclitaxel have established activity in metastatic pancreatic cancer, but alternating these specific regimens as induction is a relatively novel approach with limited prior data.

Eligibility criteria

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.

Where this trial is running

Bay Shore, New York and 6 other locations

• Imbert Cancer Center — Bay Shore, New York, United States (Recruiting)
• Northern Westchester Cancer Center — Mount Kisco, New York, United States (Recruiting)
• Long Island Jewish Medical Center — New Hyde Park, New York, United States (Recruiting)
• Zuckerberg Cancer Center — New Hyde Park, New York, United States (Recruiting)
• Manhattan Eye, Ear and Throat Hospital — New York, New York, United States (Recruiting)
• NHPP Medical Oncology at Rego Park — Rego Park, New York, United States (Recruiting)
• Phelps Cancer Center — Sleepy Hollow, New York, United States (Recruiting)

Study contacts

• Study coordinator: GI Trial Referral

Conditions Pancreatic Ductal Adenocarcinoma