BACKGROUND: The dose of bevacizumab necessary to optimally inhibit tumor angiogenesis in advanced renal cell carcinoma is unknown. In this phase II trial, we evaluated the efficacy and safety of 2 escalated doses of bevacizumab in patients with advanced clear cell renal carcinoma. PATIENTS AND METHODS: Eligible patients had metastatic or locally advanced unresectable clear cell renal carcinoma. Patients who were previously untreated or who had previously received vascular endothelial growth factor receptor (VEGFR)-targeted therapy were eligible and were considered separately in the efficacy evaluation. Two doses of bevacizumab were evaluated in sequential cohorts: 15 mg/kg every 2 weeks and 15 mg/kg weekly. The initial reevaluation was at 8 weeks; responding and stable patients continued treatment, with reevaluations every 8 weeks until tumor progression or unacceptable toxicity occurred. RESULTS: One hundred nineteen eligible patients were enrolled and received bevacizumab 15 mg/kg every 2 weeks (n = 61) or bevacizumab 15 mg/kg weekly (n = 58). Seventy patients were previously untreated with VEGFR-targeted therapy. In previously untreated patients, the overall response rate was 19%, with a median progression-free survival (PFS) of 7.8 months. Less activity was seen in patients previously treated with VEGFR-targeted agents (overall response rate, 4%; median PFS, 3.7 months). There was no suggestion of any difference in efficacy between the 2 dose levels tested. Both dose levels were tolerated well by most patients, with a spectrum of toxicity typical for bevacizumab. Grade 3/4 proteinuria was more frequent with both of these escalated doses, particularly with 15 mg/kg weekly. CONCLUSION: Although administration of escalated doses of bevacizumab was feasible in patients with advanced clear cell renal carcinoma, there was no suggestion that these doses were more efficacious than bevacizumab administered at the standard dose of 10 mg/kg every 2 weeks.