{"entity":{"id":"conko-003","kind":"trial","name":"CONKO-003 (OFF)","aka":["CONKO 003","OFF regimen trial","Oxaliplatin, folinic acid and fluorouracil second line"],"tldr":"CONKO-003 was the first randomised trial to show a second-line chemotherapy helps in pancreatic cancer: adding oxaliplatin to fluorouracil after gemcitabine failed lengthened median survival from 3.3 to 5.9 months, which is why oxaliplatin-based second-line treatment is in the NICE guideline. A later Canadian trial with a different oxaliplatin schedule found the opposite.","summary":"CONKO-003 randomised 168 patients whose disease had progressed on gemcitabine monotherapy to OFF (oxaliplatin 85 mg/m2 on days 8 and 22 with folinic acid and 24-hour fluorouracil on days 1, 8, 15 and 22 of a 42-day cycle) or FF alone, stratified by metastases, duration of first-line therapy and Karnofsky status. With a median follow-up of 54.1 months, median overall survival was 5.9 months (95 percent confidence interval 4.1 to 7.4) with OFF against 3.3 months (2.7 to 4.0) with FF (hazard ratio 0.66, 0.48 to 0.91; p 0.010) and time to progression 2.9 against 2.0 months (hazard ratio 0.68); adverse events were similar apart from grade 1 to 2 neurotoxicity (38.2 against 7.1 percent). PANCREOX (108 Canadian patients, 2016) then found modified FOLFOX6 no better for progression-free survival and worse for overall survival than infusional fluorouracil and leucovorin (6.1 against 9.9 months; p 0.02) with grade 3 to 4 events in 63 against 11 percent, so the oxaliplatin schedule matters. NICE NG85 recommends oxaliplatin-based second-line chemotherapy for people who have not had first-line oxaliplatin (1.9.7) and gemcitabine-based treatment after first-line FOLFIRINOX (1.9.8); daraxonrasib (RASolute 302) now supersedes both where it is available.","status":"positive","asOf":"2026-09-24","links":[{"label":"ClinicalTrials.gov NCT00786058","url":"https://clinicaltrials.gov/study/NCT00786058"},{"label":"Oettle et al., CONKO-003 (JCO 2014)","url":"https://doi.org/10.1200/JCO.2013.53.6995"},{"label":"Gill et al., PANCREOX (JCO 2016)","url":"https://doi.org/10.1200/JCO.2016.68.5776"}],"tags":[],"related":[],"cancers":["pancreatic","metastatic-pdac","locally-advanced-pdac"],"sections":[],"technologies":["cytotoxic-chemotherapy","platinum"],"targets":[],"drugs":["oxaliplatin","fluorouracil","leucovorin","folfox"],"companies":[],"institutions":["charite"],"pathways":[],"terms":["peripheral-neuropathy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00786058","phase":"3","setting":"Advanced pancreatic cancer progressing during first-line gemcitabine in Germany: oxaliplatin with folinic acid and fluorouracil (OFF) against folinic acid and fluorouracil (FF), with overall survival as the primary endpoint","sponsor":"Charite University Medicine Berlin (CONKO study group)","result":"Median overall survival 5.9 months with OFF against 3.3 months with FF (hazard ratio 0.66, 95 percent confidence interval 0.48 to 0.91; p 0.010); time to progression 2.9 against 2.0 months.","yearReported":2014,"enrolled":168,"enrolledBasis":"randomised","enrolledNote":"ClinicalTrials.gov NCT00786058 gives no enrolment figure in the summary record read on 24 September 2026; 168 patients were randomised at 16 German institutions between January 2004 and May 2007 and 160 were eligible for the primary analysis.","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"OFF (oxaliplatin, folinic acid, fluorouracil)","value":5.9,"note":"95% CI 4.1 to 7.4; 160 patients in the primary analysis"},{"name":"FF (folinic acid, fluorouracil)","value":3.3,"note":"95% CI 2.7 to 4.0"}],"hr":0.66,"ci":[0.48,0.91],"p":"0.010","source":"https://doi.org/10.1200/JCO.2013.53.6995"}]},"route":"/trials/conko-003/","neighbours":{"cancer":[{"id":"locally-advanced-pdac","kind":"cancer","name":"Locally advanced unresectable pancreatic ductal adenocarcinoma","route":"/cancers/locally-advanced-pdac/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"leucovorin","kind":"drug","name":"Leucovorin (folinic acid)","route":"/drugs/leucovorin/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"}],"institution":[{"id":"charite","kind":"institution","name":"Charité Universitätsmedizin Berlin","route":"/institutions/charite/"}],"term":[{"id":"pancreatic-failed-programmes","kind":"term","name":"Pancreatic cancer: the failed and stopped programmes and why","route":"/terms/pancreatic-failed-programmes/"},{"id":"peripheral-neuropathy","kind":"term","name":"Peripheral neuropathy (chemotherapy-induced)","route":"/terms/peripheral-neuropathy/"}],"trial":[{"id":"rasolute-302","kind":"trial","name":"RASolute 302","route":"/trials/rasolute-302/"}]}}