NCT00631371.

Study characteristics
Methods	Study name: INTORACT Study design: randomised, phase III Blinding: none, open‐label Study dates: April 10, 2008 ‐ October 19, 2010 (date of randomisation) Date of data cut‐off: April 19, 2012 Location: 30 countries (Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, France, Germany, Hong Kong, Hungary, India, Italy, Republic of Korea, Malaysia, Mexico, Netherlands, Poland, Portugal, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Taiwan, Ukraine, UK., USA), types of centres: hospitals, university hospitals, cancer centres, research centres (172 study locations) Cross‐ over study or cross over permitted: not per design; not reported whether cross over was permitted at some point (e.g. upon progression)
Participants	Inclusion criteria: all sexes 18 years and older histologically and/or cytologically confirmed to have advanced (stage IV or recurrent) renal cell carcinoma (RCC) majority component of conventional clear‐cell type is mandatory at least 1 measurable lesion (per RECIST) Karnofsky performance status >70%, life expectancy > 12 weeks adequate organ function written consent Exclusion criteria: prior systemic treatment for RCC evidence of current or prior central nervous system (CNS) metastases cardiovascular disease, history of major thrombotic or bleeding episode within 6 months, inadequately controlled hypertension (systolic blood pressure>150 mmHg and/or diastolic blood pressure >100 mmHg on medication) pregnant or nursing women additional criteria applies major surgery or radiation therapy within 4 weeks, or chronic use of antiplatelet agents or corticosteroids Sample size: N = 791 Age (years, median with range): experimental arm: 59 (22‐87), control arm: 58 (23‐81) Sex (m/f, %): experimental arm: 286/114, control arm: 270/121 Prognostic factors: MSKCC prognostic group, n(%) Favourable experimental arm: 123 (31), control arm: 114 (29) Intermediate experimental arm: 230 (58), control arm: 237 (61) Poor experimental arm: 47 (12), control arm: 40 (10) Prior nephrectomy n(%) Yes experimental arm: 338 (85), control arm: 335 (86)
Interventions	Experimental arm (n = 400): Bevacizumab (10 mg/kg, intravenous, every two weeks) + Temsirolimus (25mg, intravenous, once/week) Control arm (n = 391): Bevacizumab (10 mg/kg, intravenous, every two weeks) + IFN‐alfa (9 MIU, subcutaneous, three times/ week)
Outcomes	Primary outcome(s) PFS: independent‐assessment Time frame: baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks Secondary outcome(s) PFS: investigator‐assessment Time frame: baseline until disease progression, initiation of new anticancer treatment, or death, assessed every 8 weeks OS Time frame: baseline until death due to any cause, assessed every 8 weeks Safety (AE, SAE) QoL number of participants who discontinued treatment due to an AE Relevant to this review but not reported: TFST Other outcomes (not relevant to this review): ORR
Notes	Funding Sources: Brian I. Rini, Pfizer Declarations of Interests: Quote: "Although all authors completed the disclosure declaration, the following author(s) and/or an author’s immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article (...)For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors." Clinical study report available: no Study protocol available: no Statistical analysis plan available: no