Intraperitoneal paclitaxel plus NALIRIFOX for pancreatic cancer that has spread to the peritoneum

Intraperitoneal Paclitaxel With Standard Systemic NALIRIFOX for Pancreatic Ductal Adenocarcinoma With Peritoneal Carcinomatosis: Prospective Pilot Trial

This trial tests whether giving paclitaxel into the abdomen together with intravenous NALIRIFOX is safe and helps adults whose pancreatic cancer has spread to the peritoneum.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT07030283 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial combines intraperitoneal (IP) paclitaxel delivered through an abdominal catheter with intravenous NALIRIFOX given every two weeks to adults with pancreatic ductal adenocarcinoma and peritoneal carcinomatosis. Participants will have an implanted IP port and receive IP paclitaxel on days 1 and 8 of each 14-day cycle while receiving NALIRIFOX IV every two weeks, with clinic visits for labs and safety monitoring. The main goals are to determine tolerability and identify dose-limiting toxicities, with imaging and blood tests used to capture any early signs of anti-tumor activity. Treatment eligibility is limited to patients without metastases to other organs and with limited peritoneal disease burden.

Who should consider this trial

Good fit: Adults (18+) with histologically confirmed pancreatic adenocarcinoma and proven peritoneal seeding but no other-organ metastases, a PCI score ≤8, ECOG 0–1, a primary tumor that is resectable/borderline resectable/locally advanced per NCCN, and limited prior treatment (0–4 months of FOLFIRINOX/mFOLFIRINOX or NALIRIFOX) are ideal candidates.

Not a fit: Patients with metastases outside the peritoneum, PCI >8, ECOG ≥2, inadequate blood counts or organ function, inability to receive an intraperitoneal catheter, or extensive prior therapy are unlikely to benefit from this Phase 1 regimen.

Why it matters

Potential benefit: If the combination is safe and active, it could improve control of peritoneal disease and provide an additional treatment option that may delay progression for affected patients.

How similar studies have performed: Intraperitoneal paclitaxel has shown promising signals for peritoneal carcinomatosis in other cancers, but combining IP paclitaxel with systemic NALIRIFOX for pancreatic cancer is largely novel and not yet established.

Eligibility criteria

Inclusion Criteria:

1. Provision to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the duration of the study.
3. Be age 18 years or older.
4. Histologically or cytologically confirmed pancreatic adenocarcinoma with histologically or cytologically proven seeding in the peritoneal cavity without metastasis to other organs.
5. Primary tumor that is resectable, borderline resectable, or locally advanced per NCCN classification.
6. PCI score ≤ 8.
7. ECOG performance status of 0 or 1
8. Prior treatment for 0-4 months with FOLFIRINOX, modified FOLFIRINOX, or NALIRIFOX and able to receive additional treatment per investigator opinion
9. Adequate biological parameters as evidenced by all of the following blood counts:

   * Absolute neutrophil count (ANC) \>/= 1,500 per cubic millimeter without the use of hematopoietic growth factors within 14 days prior to screening
   * Platelet count \>/= 75,000 per cubic millimeter
   * Hemoglobin \> 9 g/dL
10. Adequate hepatic function as evidenced by:

    * Serum total bilirubin ≤ 1.5x ULN (biliary drainage is allowed for biliary obstruction), and
    * AST and ALT ≤ 3 x ULN
11. Adequate renal function as evidenced by serum creatinine \<1.5 x ULN

Exclusion Criteria:

1. Prior treatment of pancreatic cancer in the metastatic setting with surgery or investigational therapy (Note: biliary drainage, diagnostic laparoscopy/laparotomy, and duodenal stenting is allowed).
2. Evident distant metastatic disease outside of the peritoneal cavity.
3. Extensive metastatic disease in peritoneal cavity (PCI\>8).
4. Known disease progression with any prior chemotherapy.
5. Known hypersensitivity to paclitaxel or other liposomal products.
6. Current use of strong CYP2C8 inhibitors or inducers, or presence of any other contraindications for paclitaxel.
7. Known UGT1A1 deficiency or DPD deficiency.
8. Neuropathy Grade 2 or higher
9. Known active COVID infection with symptoms.
10. Has ever received or is currently receiving radiation for pancreatic cancer treatment.
11. Receipt of live, attenuated vaccine within 30 days prior the first dose of Intraperitoneal paclitaxel. (Note: enrolled patients should not receive live vaccines during the study and up to 30 days after the last dose of intraperitoneal paclitaxel).
12. Known positive test results for human immunodeficiency (HIV) or patients with chronic or active hepatitis B or C. Patients who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA after anti-viral therapy may be enrolled.
13. Active infection during screening visits or on the day of treatment, which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome.
14. Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
15. Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy within 7 days prior to C1D1. Both male and female patients of reproductive potential must agree to use a highly effective method of birth control during the study and for 9 months following the last dose of both IP PTX and IV NALIRIFOX.
16. Histologies other than adenocarcinoma, such as neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma.
17. Patients who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.

Where this trial is running

Aurora, Colorado

• University of Colorado Cancer Center — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Alexis Leal, MD — University of Colorado, Denver
• Study coordinator: Puja Gupta Poddar

Conditions Pancreatic Ductal Adenocarcinoma; Peritoneal Carcinomatosis; pancreatic adenocarcinoma; pancreatic ductal adenocarcinoma; PDAC; metastatic; NALIRIFOX; intraperitoneal chemotherapy