What type of study is this?

This is a Pre-Registered Trial study.

What question did this study set out to answer?

To evaluate the efficacy and safety of NALIRIFOX in patients with metastatic small bowel adenocarcinoma.

January 14, 2026

Phase II study of NALIRIFOX (nanoliposomal irinotecan + oxaliplatin with fluorouracil and folinic acid) in advanced unresectable small bowel tumors.

Key Points

To evaluate the efficacy and safety of NALIRIFOX in patients with metastatic small bowel adenocarcinoma.
Phase II, single arm, multicenter trial
Using Bayesian predictive probability to assess response rate
Targeting 36 participants in total
Treatment includes nal-IRI, oxaliplatin, fluorouracil, and leucovorin over 28-day cycles
Expected response rate of ≥40% for further investigation
Key inclusion includes measurable disease and ECOG 0-1
Primary endpoints are overall response rate; secondary endpoints include safety, duration of response, progression-free survival, and overall survival

Abstract

TPS802 Background: Small bowel cancers account for 3% of all gastrointestinal malignancies and small bowel adenocarcinoma (SBA) represents 40% of this population. SBA has a poor prognosis, with 5-year overall survival (OS) rates of 3.0% to 19.0% for metastatic disease. SBA is mostly diagnosed in the late stage and there is no standard first-line (1L) chemotherapy approach for patients with advanced SBA. Few prospective non-randomized phase II studies have been reported and encouraging results were seen with capecitabine and oxaliplatin (CAPOX) revealing response rate (RR) 52% and median overall survival (OS) 15.5 months (mo); and 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) with RR 45% and OS 17.3 mo. Nanoliposomal irinotecan (nal-IRI) is composed of pegylated liposomal particles encapsulating an irinotecan sucrosofate salt payload, which extends the circulation of irinotecan before metabolic conversion to SN‐38, resulting in an improved pharmacokinetic profile. In the phase III NAPOLI-3 trial in 1L for pancreatic cancer, the NALIRIFOX (nal-IRI, oxaliplatin, fluorouracil and folinic acid) significantly improved OS and progression-free survival (PFS) compared to nab-paclitaxel plus gemcitabine. Here, we propose a prospective phase II trial of NALIRIFOX in metastatic or unresectable SBA. Methods: This is a phase II, single arm, multicenter trial. A two-stage design using Bayesian predictive probability will be used to evaluate the RR in participants with metastatic SBA receiving NALIRIFOX. The first stage will enroll 18 participants for futility analysis. If 4 or more responses are seen, the trial will enroll 18 additional participants for a total of 36. We consider that a RR ≥ 40% is worthy for further investigation while a RR < 20% indicates treatment ineffectiveness. Treatment will be given on Day 1 and Day 15 of each 28-day cycle consisting of the following: nal-IRI 50 mg/m 2 , followed by oxaliplatin 60 mg/m 2 , followed by leucovorin at 400 mg/m 2 and 5-FU 2400 mg/m 2 over 46 hours continuously. Key inclusion criteria include mismatch repair proficient tumor, measurable disease, ECOG 0-1 and no prior treatment for metastatic disease. Ampullary or appendiceal tumors, neuroendocrine or any other histology different than SBA or known low/absent dihydropyridine dehydrogenase (DPD) activity are key exclusion criteria. Primary endpoints are ORR and secondary endpoints include safety, duration of response, PFS and OS. This trial is conducted through the Hoosier Cancer Research Network under HCRN-GI23-617 and registered on clinicaltrials.gov under NCT06835387. Clinical trial information: NCT06835387 .

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