Surgery to remove pancreatic cancer and a few liver or lung metastases

Surgical Resection of Synchronous Pulmonary or Hepatic Oligometastatic Pancreatic Ductal Adenocarcinoma (PHOLIPANC) Following Pre-operative Liposomal Irinotecan Combined With Oxaliplatin and 5-Fluoracil/Folinic Acid (NALIRIFOX): A Phase II Open-Label Single Arm Trial

This trial tests whether giving NALIRIFOX chemotherapy first and then surgically removing the main pancreatic tumor and limited liver or lung metastases helps people with pancreatic cancer that has only a few metastases.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sex: All
• Sponsor: The University of Texas Health Science Center at San Antonio (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT07340151 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm surgical trial for patients with treatment‑naïve pancreatic adenocarcinoma and a limited number of liver or lung metastases. All participants receive neoadjuvant NALIRIFOX chemotherapy and are re-evaluated after four cycles; those with progression are removed from the protocol while those with response or stable disease are considered for resection. Patients with a technically resectable primary tumor proceed to exploratory laparotomy and synchronous or staged resection of the primary and metastatic lesions 2–6 weeks after finishing chemotherapy; if the primary is found unresectable at surgery, additional systemic therapy may be given. Imaging must show 1–5 potentially resectable hepatic metastases or limited pulmonary metastases, and decisions are made by an interdisciplinary tumor board and the operating surgeon.

Who should consider this trial

Good fit: Ideal candidates are treatment‑naïve adults with pancreatic ductal adenocarcinoma and 1–5 resectable liver or limited lung metastases who can tolerate NALIRIFOX chemotherapy and major surgery and who have response or stable disease after four cycles.

Not a fit: Patients with widespread metastases (>5 lesions), disease progression during the initial four cycles, an unresectable primary tumor, or who are unfit for major surgery are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, combining NALIRIFOX chemotherapy with surgical removal of both the primary tumor and limited metastases could improve survival and offer durable disease control for a selected group of patients.

How similar studies have performed: Retrospective series and limited prospective efforts suggest select patients with oligometastatic pancreatic cancer may achieve prolonged survival after metastasis-directed surgery, but high-quality randomized evidence is scarce and the specific combination with NALIRIFOX is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed diagnosis of treatment-naïve limited hepatic or pulmonary metastatic adenocarcinoma of the pancreas
2. Meet the definition of limited hepatic or pulmonary metastasis according to Computed Tomography/Magnetic Resonance Imaging (CT/MRI) that is done prior to the starting of any anticancer treatment. Either CT scan of chest, abdomen, and pelvis with intravenous contrast or a combination of MRI of abdomen and pelvis and CT scan of chest is acceptable radiographic imaging. CT/MRI can be done at an outside facility but must be reviewed by a local radiologist.

   * Definition of limited hepatic metastasis: 1 to 5 metastases in CT/MRI, which are potentially resectable or treatable by ablative procedures.

     * Note 1: Patients also fulfil this inclusion criterion if a hepatic metastasis was partly or entirely removed as part of the diagnosis and is thus not detectable by CT/MRI scan at screening.
     * Note 2: If more than 5 metastases are unexpectedly detected during surgery, it is not a violation of this inclusion criterion if the excess metastases had not been detectable by CT/MRI scan at screening.
   * Definition of limited pulmonary metastasis: 1 to 4 pulmonary nodules seen on CT/MRI, suspicious for pulmonary metastases as per the multidisciplinary tumor board radiologist and surgeon.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
4. Patients ≥18 years at the time of signing the informed consent
5. Being a candidate for chemotherapy with NALIRIFOX
6. Patient's written informed consent prior to any trial-specific procedure
7. Patient's legal capacity to consent to participation in the clinical trial.

Exclusion Criteria:

1. Acinar cell carcinoma and/or neuroendocrine carcinoma of the pancreas
2. Symptomatic clinically significant ascites
3. Evidence of any distant metastases other than limited hepatic or pulmonary metastasis as defined in inclusion criterion 1.
4. Evidence of simultaneous pulmonary and hepatic metastases
5. Any tumor-specific pretreatment of the adenocarcinoma of the pancreas (including but not limited to surgery, radiation therapy, chemotherapy or ablative procedures). Currently being on NALIRIFOX or its modified form is allowed, unless more than 2 treatments of NALIRIFOX have been given.
6. Any malignancies other than adenocarcinoma of the pancreas in the 2 years before the start of the clinical trial except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, breast cancer, prostate cancer or superficial bladder tumors (Ta, Tis and T1 staging where Ta=non-invasive; Tis=high-grade, flat non-invasive cancer in situ; T1=relatively small primary tumor that has not spread to surrounding tissues)
7. Known Human immunodeficiency virus (HIV) seropositivity
8. Known active or chronic Hepatitis B or Hepatitis C infection
9. Known glucuronidation deficiency (Gilbert's syndrome)
10. Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the clinical trial and his/her safety during the trial or interfere with interpretation of results, e.g., severe hepatic, renal, pulmonary, cardiovascular, metabolic or psychiatric disorders

Where this trial is running

San Antonio, Texas

• The University of Texas Health Science Center San Antonio — San Antonio, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Lei Zheng, MD, PhD — The University of Texas Health Science Center at San Antonio
• Study coordinator: Lei Zheng, MD, PhD

Conditions Adenocarcinoma of the Pancreas; Oligometastatic disease; Hepatic oligometastatic adenocarcinoma of the pancreas; Pulmonary oligometastatic adenocarcinoma of the pancreas; Surgical resection