NCT00065468.

Study characteristics
Methods	Study name: ‐ Study design: randomised, phase III (three‐arm trial) Blinding: none, open‐label Study dates: July 2003 – April 2005 (date of enrolment) Date of data cut‐off: exact date not reported. The results presented and used in this review are of the second interim analysis. Location: 25 countries (Argentina, Australia, Canada, Czech Republic, Former Serbia and Montenegro Germany, Greece, Hungary, Italy, Latvia, Lithuania, Mexico, the Netherlands, Poland, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, UK, USA; types of centres: cancer centres, hospitals, university hospitals (153 study locations) Cross‐over study or cross‐over permitted: no
Participants	Inclusion criteria: all sexes 18 years and older histologically confirmed, advanced RCC no prior systemic therapy Exclusion criteria: participants with central nervous system (CNS) metastases prior anticancer therapy for RCC prior investigational therapy/agents within 4 weeks of randomisation Sample size: N = 626 Age, median in years (range): experimental arm I: 60 (23‐86), experimental arm II arm: 58 (32‐81), control arm: 59 (32‐82) Sex (m/f): experimental arm I: 148/59, experimental arm II: 139/70, control arm: 145/65 Prognostic factors: MSKCC risk classification, n (%) Poor risk (≥3 of 5 factors) experimental arm I: 157 (76), experimental arm II: 145 (69), control arm: 160 (76) Intermediate risk(1 or 2 or 5 factors) experimental arm I: 50 (24), experimental arm II: 64 (31), control arm: 50 (24) Previous nephrectomy (N,%) Yes experimental armI: 193 (67), experimental arm II: 168 (80), control arm: 141 (67)
Interventions	Experimental arm I (n = 207): Interferon alfa, 3 MIU (1st week), 9 MIU (2nd week), 18 MIU (thereafter) (subcutaneous injection, three times/week) Experimental arm II (n = 209): Temsirolimus (25 mg, intravenous, once/week) Control arm (n = 210): Interferon alfa 3 MIU (1st week), 6 MIU (thereafter) (subcutaneous injection, three times/week) + Temsirolimus (15 mg, intravenous, once/week)
Outcomes	Primary outcome(s) OS Time frame: baseline up to month 80 Secondary outcome(s) PFS Time frame: at baseline, monthly until tumour progression or death (up to month 80) Quality of life, measured with the European Quality of Life Health Questionnaire (EQ‐5D) ‐ Index Score time frame: measured at baseline Safety (AEs, SAEs) Relevant to this review but not reported: TFST; number of participants who discontinued treatment due to an AE Other outcomes (not relevant to this review): objective response (OR); participants with clinical benefit; duration of response (DR); time to treatment failure (TTF); quality‐adjusted time without symptoms or toxicity (Q‐TWIST)
Notes	Funding sources: Pfizer Declarations of Interests: Quote: "Dr. Hudes reports receiving consulting and lecture fees from Pfizer Pharmaceuticals and consulting fees from Wyeth Pharmaceuticals; Drs. Carducci and Motzer, consulting fees from Wyeth Pharmaceuticals; Dr. Dutcher, consulting and lecture fees from Novartis, Chiron, Bayer, and Onyx Pharmaceuticals, consulting fees from Wyeth Pharmaceuticals, lecture fees from Pfizer Pharmaceuticals, and research grants from Bayer, Chiron, Genentech, Pfizer, and Wyeth Pharmaceuticals; Dr. Figlin, consulting and lecture fees and research grants from Wyeth Pharmaceuticals; Dr. Kapoor, consulting fees and research grants from Wyeth Pharmaceuticals and research grants from Bayer Pharmaceuticals; Dr. McDermott, consulting fees from Bayer, Onyx, and Genentech Pharmaceuticals and lecture fees from Novartis Pharmaceuticals; and Dr. Schmidt‐Wolf, symposium support fees from Wyeth Pharmaceuticals. Mr. O’Toole, Ms. Lustgarten, and Dr. Moore report being full‐time employees of Wyeth Pharmaceuticals. No other potential conflict of interest relevant to this article was reported." Clinical study report available: no Study protocol available: no Statistical analysis plan available: no