NCT02761057.

Study characteristics
Methods	Study name: SWOG 1500 Study design: RCT, phase II Blinding: none, open‐label Study dates: April 5, 2016 ‐ Dec 15, 2019 (date of randomisation) Date of data cut‐off: October 16, 2020 (for first analysis); exact date for updated analyses not reported Location: 2 countries (Canada, U.S.A.), types of centres: cancer centres, medical centres, hospitals, (597 study locations) Cross‐over study or cross over permitted: not per design; not reported whether cross over was allowed at some point (e.g. at progression)
Participants	Inclusion / exclusion criteria: Patients must have histologically or cytologically confirmed papillary renal cell carcinoma which is metastatic or locally advanced disease not amenable to surgical resection Patients must also have measurable disease Patients with a history of treated brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti‐seizure medications are allowed provided they are non‐enzyme Patients may have received prior surgery; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery Patients may have received up to one prior systemic therapy* for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)‐approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 14 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration More inclusion & exclusion criteria on CT.gov. Sample size: N=147 Age, median (years, range): 66 (58‐75) (across all participants) Sex (m/f): 112 females; 35 males (across all participants) Prognostic factors: IMDC prognostic risk group, n(%) Favourable experimental arm I: 10 (23), experimental arm II: 8 (29), experimental arm III: 6 (21) control arm: 14 (30) Intermediate experimental arm I: 28 (64), experimental arm II: 16 (57), experimental arm III: 19 (66), control arm: 26 (75) Poor experimental arm I: 6 (14), experimental arm II: 4 (14), experimental arm III: 4 (14), control arm: 6 (13) Previous nephrectomy, n(%) Yes experimental arm: 32 (73), experimental arm II: 26 (93), experimental arm III: 21 (72), control arm: 34 (77)
Interventions	Experimentarl arm I (N = 46): sunitinib (50 mg, oral, once/day) ‐ treatment was 4 weeks on treatment, 2 weeks off treatment (1 cycle = 6 weeks) Experimental arm II (N = 44): cabozantinib (60 mg, oral, once/day) Experimental arm III (N = 28): crizotinib (250 mg, oral, twice/day) Experimental arm IIII (N = 29): savolitinib (600 mg, oral, once/day)
Outcomes	Primary outcome(s) PFS Secondary outcome(s) Toxicity OS Number of participants who discontinued study drug due to an AE Relevant to this review but not reported: QoL, TFST Other outcomes (not relevant to this review): ORR
Notes	Funding sources: National Institutes of Health and National Cancer Institute. Declaration of Interest: yes Clinical study report available: no Study protocol available: yes Statistical analysis plan available: Other: *7% of the study population received one prior line of systemic therapy (excluding VEGF‐directed or MET‐directed drugs).