Clarke 2011.

Methods	Randomized controlled trial Phase II, multicenter
Participants	Incurable locally advanced or metastatic CRC, progressive disease after one prior chemotherapy regimen for advanced disease and/or after prior adjuvant therapy, provided that relapse had occurred within 6 months of that treatment
Interventions	IRI + 5‐FU/LV vs IRI
Outcomes	Overall survival Progression‐free survival Toxicity
Notes	Trial was terminated due to slow recruitment. Similar efficacy between the two arms but IRI + 5‐FU/LV had slightly less toxicities
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Minimisation
Allocation concealment (selection bias)	Low risk	Central randomization/allocation by telephone
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No mention of blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No mention of blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Four patients withdrew early (2 in the intervention and 2 in the control arm). Three withdrew before baseline tumour assessment and did not receive any treatment. The fourth one opted 3 days after consent to receive off‐study irinotecan and cetuximab. These patients were included in the analysis, except one who explicitly refused.
Selective reporting (reporting bias)	Unclear risk	No reported pre‐specified outcomes
Other bias	Low risk	None