Reichle 2007.

Study characteristics
Methods	Phase II parallel‐group RCT. Open label study.
Participants	Untreated metastatic melanoma. Participants randomised: 76.
Interventions	Two‐arm trial: Trofosfamide 50 mg orally 3 times daily for a maximum of 6 weeks (N = 32); Trofosfamide 50 mg orally 3 times daily, rofecoxib 25 mg orally, and pioglitazone 60 mg orally for a maximum of 6 weeks (N = 35).
Outcomes	Progression‐free survival. Overall survival. Tumour response. Toxicity.
Notes	Cross‐over: cross‐over to combination therapy was allowed at disease progression. Quality of life: not reported. Participants with brain metastasis: included (quote: "controlled brain metastasis"). Median follow‐up: not available.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomised". Comment: There was insufficient information about the sequence generation process to permit judgment.
Allocation concealment (selection bias)	Unclear risk	There was insufficient information to permit judgment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	As an open label study, no blinding of participants or personnel was possible. However, we believe that in this setting (metastatic melanoma), with the treatments tested and outcomes assessed, the knowledge of which intervention was received or administered (rather than the intervention itself), could not affect the outcomes under investigation. Therefore, we judged the risk of performance bias as low.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	There was insufficient information to permit judgment.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data were balanced across intervention groups, with similar reasons for missing data across groups.
Selective reporting (reporting bias)	Low risk	No differences between protocol and published report.
Other bias	Low risk	The study appeared to be free of other sources of bias.