NCT01217931.

Methods	Study type: randomised, phase II study Blinding: no, open‐label Study dates: January 2011 ‐ January 2022 (final data collection date for primary outcome measures) Cross‐over study: sequential two‐agent assessment Status: active, not recruiting (as of May 4, 2022)
Participants	Estimated enrolment: 240 Risk groups: no information Inclusion criteria: confirmed metastatic RCC with a clear cell component prior radical or partial nephrectomy required. Participants whose primary tumour was treated with cryoablation or radiofrequency ablation would also be eligible measurable disease Age >/= 18 years ECOG performance status 0 or 1 adequate organ and marrow function within 14 days (see CT.gov for specifics) non‐pregnant female participants participants of child fathering or childbearing potential must be on birth control while on study participants must give written informed consent prior to initiation of study‐related procedures. participants with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy Exclusion criteria: no patient with any concurrent active malignancy, i.e. a patient requiring or receiving systemic therapy for another malignancy at the same time of treatment for RCC participants must not have received any prior targeted therapy (anti‐VEGF agents or mTOR inhibitors), including adjuvant therapy, and must not have received any prior chemotherapy for mRCC. However, participants who had received prior immunotherapy, such as cytokines or vaccines, are permitted to enrol. participants must not be scheduled to receive another experimental drug while on this study. Participants are permitted to receive concomitant bisphosphonates. participants must not have multiple brain metastases or leptomeningeal disease. Participants with controlled solitary brain metastasis are eligible. More exclusion criteria on CT.gov.
Interventions	Group 1: Pazopanib + possible Bevacizumab Group 2: Pazopanib + possible Everolimus Group 3: Everolimus + possible Bevacizumab Group 4: Everolimus + possible Pazopanib Group 5: Bevacizumab + possible Pazopanib Group 6: Bevacizumab + possible Everolimus
Outcomes	Primary outcome(s) ‐ Secondary outcome(s) ‐ Outcomes relevant to this review but not to be assessed: PS, PFS, TFST, AE, SAE, QoL, number of participants who discontinued treatment due to an AE Other outcomes to be assessed (not relevant to this review): time to overall treatment failure
Notes	Prior systemic therapy:quote: "participants must not have received any prior targeted therapy (anti‐VEGF agents or mTOR inhibitors), including adjuvant therapy, and must not have received any prior chemotherapy for mRCC. However, participants who had received prior immunotherapy, such as cytokines or vaccines, are permitted to enroll." ‐‐> Awaiting results to check number of participants with prior immunotherapy (if any), and whether results are reported separately for the treatment‐naive participants. Funding sources: M.D. Anderson Cancer Center, Novartis