Wasan COIN‐B 2014.
| Methods | Phase II randomised, open‐label trial; n = 226 (169 KRAS exon 2 WT) | |
| Participants | People with advanced colorectal cancer, no prior chemotherapy for metastases | |
| Interventions | Intermittent mFOLFOX6 with cetuximab (ceased after 12 weeks; assuming stable disease or better, re‐introduction of mFOLFOX6 with cetuximab on progression) versus continuous mFOLFOX6 with cetuximab (same as intermittent mFOLFOX6 with cetuximab, with maintenance cetuximab in between periods of mFOLFOX6 with cetuximab) | |
| Outcomes | Primary outcome: failure‐free survival at 10 months (in participants who had completed initial 12 weeks of mFOLFOX6 with cetuximab). Main secondary outcomes: Overall survival, progression‐free survival in the interval | |
| Notes | Funded by UK Medical Research Council and Merck KGaA. Wasan: advisory boards, educational meetings (as faculty and speaker) for Merck KGaA. TM: grants, personal fees, non‐financial support from Merck KGaA unrelated to this study Follow‐up 32.8 months in intermittent cetuximab group, 34.2 months in continuous cetuximab group |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | The MRC Clinical Trials Unit did the randomisation by telephone, using the method of minimisation with a random element. The minimisation factors were hospital, WHO performance status, previous adjuvant chemotherapy, liver metastases, and peritoneal metastases. Participants were randomly assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or intermittent chemotherapy plus continuous cetuximab. |
| Allocation concealment (selection bias) | High risk | Treatment allocation was not masked. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Open‐label trial |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | "We did not confirm responses with repeat scans nor did we do central radiological review." |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 3/130 participants in primary outcome population lost to follow‐up |
| Selective reporting (reporting bias) | High risk | Data for KRAS exon 2 MT participants not yet published; quality of life data not yet published |
| Other bias | Low risk | No other significant bias present |