{"entity":{"id":"nifty","kind":"trial","name":"NIFTY","aka":[],"tldr":"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.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT03524508","url":"https://clinicaltrials.gov/study/NCT03524508"},{"label":"Yoo et al., Lancet Oncology 2021: NIFTY","url":"https://doi.org/10.1016/S1470-2045(21)00486-1"},{"label":"Hyung et al., JAMA Oncology 2023: NIFTY updated analysis","url":"https://doi.org/10.1001/jamaoncol.2023.0016"}],"tags":["lesson:replication"],"related":["naliricc","abc-06"],"cancers":["gallbladder","cholangiocarcinoma","biliary-tract-cancer"],"sections":[],"technologies":["cytotoxic-chemotherapy","topoisomerase-inhibitors"],"targets":[],"drugs":["liposomal-irinotecan","fluorouracil","leucovorin"],"companies":[],"institutions":["asan-medical-center"],"pathways":[],"terms":[],"trials":[],"people":["ghassan-abou-alfa"],"bottlenecks":[],"keyPapers":["paper-nifty-liposomal-irinotecan-lancet-oncol-2021"],"journals":[],"dependsOn":[],"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."],"nct":"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)","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).","yearReported":2021,"enrolled":178,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival by masked independent central review (updated, re-read)","unit":"months","arms":[{"name":"Liposomal irinotecan + 5-FU/LV","n":88,"value":4.2},{"name":"5-FU/LV","n":86,"value":1.7}],"hr":0.61,"ci":[0.44,0.86],"p":"0.004","source":"https://doi.org/10.1001/jamaoncol.2023.0016"},{"endpoint":"Grade 3-4 neutropenia","unit":"%","arms":[{"name":"Liposomal irinotecan + 5-FU/LV","n":88,"value":24},{"name":"5-FU/LV","n":86,"value":1}],"source":"https://doi.org/10.1016/S1470-2045(21)00486-1"}],"replication":"Not reproduced by the German NALIRICC phase 2 (2024); a 2025 pooled analysis modestly favoured the combination."},"route":"/trials/nifty/","neighbours":{"trial":[{"id":"abc-06","kind":"trial","name":"ABC-06","route":"/trials/abc-06/"},{"id":"naliricc","kind":"trial","name":"NALIRICC (AIO)","route":"/trials/naliricc/"}],"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"topoisomerase-inhibitors","kind":"technology","name":"Topoisomerase-I inhibitors (and ADC payloads)","route":"/technologies/topoisomerase-inhibitors/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"leucovorin","kind":"drug","name":"Leucovorin (folinic acid)","route":"/drugs/leucovorin/"},{"id":"liposomal-irinotecan","kind":"drug","name":"Liposomal irinotecan","route":"/drugs/liposomal-irinotecan/"}],"institution":[{"id":"asan-medical-center","kind":"institution","name":"Asan Medical Center","route":"/institutions/asan-medical-center/"}],"person":[{"id":"ghassan-abou-alfa","kind":"person","name":"Ghassan K. Abou-Alfa","route":"/people/ghassan-abou-alfa/"}],"paper":[{"id":"paper-nifty-liposomal-irinotecan-lancet-oncol-2021","kind":"paper","name":"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","route":"/key-papers/paper-nifty-liposomal-irinotecan-lancet-oncol-2021/"}],"roadmap":[{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"}],"term":[{"id":"gallbladder-cancer-in-biliary-trials","kind":"term","name":"Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups)","route":"/terms/gallbladder-cancer-in-biliary-trials/"}]}}