# NIFTY

Source: https://onco.cc/trials/nifty/  
OnCo record `nifty` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A Korean trial found that adding liposomal irinotecan to fluorouracil as second-line chemotherapy for bile duct and gallbladder cancer delayed progression, from about six weeks to four months on the re-read scans, at the cost of more neutropenia. A German trial of the same idea was negative, so it is an option rather than a standard, and it is not commissioned in the UK.

## Summary

NIFTY (NCT03524508) randomised 178 patients (174 in the full analysis set: 88 to liposomal irinotecan 70 mg/m² plus leucovorin 400 mg/m² and fluorouracil 2,400 mg/m² every two weeks, 86 to fluorouracil and leucovorin alone) with metastatic biliary tract cancer that had progressed on first-line gemcitabine and cisplatin, stratified by primary tumour site. At the primary analysis (median follow-up 11.8 months) blinded independent central review progression-free survival was 7.1 versus 1.4 months (hazard ratio 0.56, 95 percent confidence interval 0.39 to 0.81, p 0.0019). With extended follow-up and a re-performed masked central review by three new radiologists, the medians fell to 4.2 versus 1.7 months (hazard ratio 0.61, 0.44 to 0.86, p 0.004), a discordance the authors attributed to reader variation. Grade 3 to 4 neutropenia occurred in 24 versus 1 percent and serious adverse events in 42 versus 24 percent, with no treatment-related deaths. The German NALIRICC trial did not reproduce the benefit, though a pooled analysis modestly favoured the combination. NCCN lists the regimen as a second-line option; in the UK FOLFOX from ABC-06 is the commissioned second-line regimen and liposomal irinotecan is licensed only for pancreatic cancer.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Tags: lesson:replication
- Registry id: NCT03524508
- Phase: 2
- Setting: Metastatic biliary tract cancer after progression on gemcitabine and cisplatin: fluorouracil and leucovorin with or without liposomal irinotecan, open-label randomised phase 2b at five Korean centres
- Sponsor: Asan Medical Center (Changhoon Yoo)
- Enrolled: 178
- Result: BICR PFS 7.1 vs 1.4 months, HR 0.56 (0.39 to 0.81), p=0.0019; re-read PFS 4.2 vs 1.7 months, HR 0.61 (0.44 to 0.86).
- Outcomes: Progression-free survival by masked independent central review (updated, re-read): Liposomal irinotecan + 5-FU/LV 4.2 months vs 5-FU/LV 1.7 months, HR 0.61; Grade 3-4 neutropenia: Liposomal irinotecan + 5-FU/LV 24% vs 5-FU/LV 1%
- Replication: Not reproduced by the German NALIRICC phase 2 (2024); a 2025 pooled analysis modestly favoured the combination.

## Notes

- Key figures: 178 randomised (174 analysed, 88 versus 86); blinded central review progression-free survival 7.1 versus 1.4 months (hazard ratio 0.56, 0.39 to 0.81, p 0.0019) at the primary analysis and 4.2 versus 1.7 months (hazard ratio 0.61, 0.44 to 0.86, p 0.004) on the re-read with extended follow-up; grade 3 to 4 neutropenia 24 versus 1 percent; serious adverse events 42 versus 24 percent; no treatment-related deaths. Not reproduced by NALIRICC. Liposomal irinotecan is not commissioned for biliary cancer in the UK, where FOLFOX (ABC-06) is the second-line standard.

## Sources

- ClinicalTrials.gov NCT03524508: https://clinicaltrials.gov/study/NCT03524508
- Yoo et al., Lancet Oncology 2021: NIFTY: https://doi.org/10.1016/S1470-2045(21)00486-1
- Hyung et al., JAMA Oncology 2023: NIFTY updated analysis: https://doi.org/10.1001/jamaoncol.2023.0016

## Connected records

- trials: [ABC-06](https://onco.cc/trials/abc-06/), [NALIRICC (AIO)](https://onco.cc/trials/naliricc/)
- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Leucovorin (folinic acid)](https://onco.cc/drugs/leucovorin/), [Liposomal irinotecan](https://onco.cc/drugs/liposomal-irinotecan/)
- institutions: [Asan Medical Center](https://onco.cc/institutions/asan-medical-center/)
- people: [Ghassan K. Abou-Alfa](https://onco.cc/people/ghassan-abou-alfa/)
- key papers: [Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study](https://onco.cc/key-papers/paper-nifty-liposomal-irinotecan-lancet-oncol-2021/)
- roadmaps: [Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials](https://onco.cc/roadmaps/gallbladder-cancer-roadmap/)
- terms: [Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups)](https://onco.cc/terms/gallbladder-cancer-in-biliary-trials/)

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