# CONKO-003 (OFF)

Source: https://onco.cc/trials/conko-003/  
OnCo record `conko-003` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Also known as: CONKO 003; OFF regimen trial; Oxaliplatin, folinic acid and fluorouracil second line
- Registry id: 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)
- Enrolled: 168
- 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.
- Outcomes: Overall survival: OFF (oxaliplatin, folinic acid, fluorouracil) 5.9 months vs FF (folinic acid, fluorouracil) 3.3 months, HR 0.66

## Sources

- ClinicalTrials.gov NCT00786058: https://clinicaltrials.gov/study/NCT00786058
- Oettle et al., CONKO-003 (JCO 2014): https://doi.org/10.1200/JCO.2013.53.6995
- Gill et al., PANCREOX (JCO 2016): https://doi.org/10.1200/JCO.2016.68.5776

## Connected records

- cancers: [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Platinum agents](https://onco.cc/technologies/platinum/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Leucovorin (folinic acid)](https://onco.cc/drugs/leucovorin/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/)
- institutions: [Charité Universitätsmedizin Berlin](https://onco.cc/institutions/charite/)
- terms: [Pancreatic cancer: the failed and stopped programmes and why](https://onco.cc/terms/pancreatic-failed-programmes/), [Peripheral neuropathy (chemotherapy-induced)](https://onco.cc/terms/peripheral-neuropathy/)
- trials: [RASolute 302](https://onco.cc/trials/rasolute-302/)

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