Optimizing first-line NALIRIFOX and exploring the role of the microbiota in second-line pancreatic cancer treatment: the PRODIGE 105-GERCOR 116 PANORAMIX trial.

Authors

Matthieu Delaye, Marc Hilmi, Paul Gougis, Christelle d' Engremont, Julie Lavole, Pauline Vaflard, Olivier Bouché, Jean-Baptiste Bachet, Nicolas Williet, Brice Chanez, Gaël Roth, Victoire de Lastours, Victoire Cardot-Ruffino, Marie-Line Garcia Larnicol, Dewi Vernerey, Cindy Neuzillet

Published in

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. Oct 28, 2026. Epub Oct 28, 2026.

Abstract

Treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) relies on chemotherapy. Although NALIRIFOX (Nal-IRI, oxaliplatin, 5-fluorouracil [5-FU], leucovorin) improves survival, cumulative toxicity may limit duration, and maintenance strategies remain unexplored. Intratumoral microbiota, particularly Gammaproteobacteria expressing cytidine deaminase, may inactivate gemcitabine and contribute to resistance, a process potentially reversible with antibiotics. We aim to assess maintenance 5-FU after NALIRIFOX and microbiota modulation with fluoroquinolones to enhance gemcitabine sensitivity.
PANORAMIX is a multicenter, proof-of-concept, non-comparative phase II trial conducted across 18 French centers with two sequential randomizations. After 8 cycles of NALIRIFOX, patients with mPDAC are randomized (2:1) to either maintenance 5-FU or continuation of NALIRIFOX (Step 1). In Step 2, patients are randomized (1:1) to ciprofloxacin or placebo combined with gemcitabine-based chemotherapy (± paclitaxel). A total of 108 and 92 patients will be enrolled in Steps 1 and 2, respectively. Main inclusion criteria include age >18 years, confirmed mPDAC, ECOG performance status 0-1, and adequate organ function. Primary endpoints are 6-month progression-free survival (Step 1) and 6-month overall survival (Step 2). Secondary endpoints include toxicity and quality of life.
This two-step trial will address key therapeutic questions in mPDAC and support translational research.

PMID:
42951709
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.

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