| General information |
| Database: | DB00486 |
| Objective: | The dose of bevacizumab necessary to optimally inhibit tumor angiogenesis in advanced renal cell carcinoma is unknown. In thisphase II trial, they evaluated the efficacy and safety of 2 escalated doses of bevacizumab in patients with advanced clear cell renal carcinoma. |
| Authors: | Hainsworth JD, et al |
| Title: | Highdose bevacizumab in the treatment of patients with advanced clear cell renal carcinoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. |
| Journal: | Clin Genitourin Cancer. |
| Year: | 2013 |
| PMID: | 23684421 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II Trial |
| Key Patients Feature: | Patients were required to have biopsyproven metastatic or locally unresectable renal cell carcinoma, with at least 75% of the biopsyspecimen showing clear cell histologic features. Two subsets of patients were evaluated separately in this trial: (1) patients previouslyuntreated with VEGFRtargeted agents and (2) patients previouslytreated with VEGFRtargeted therapy. Patients may also have received 1 previous regimen with traditional immunotherapy, chemotherapy, or combination chemoimmunotherapy. Previous nephrectomy was required unless clinically inappropriate. Additionaleligibility criteria included Eastern Cooperative Oncology Groupperformance status of 0 to 1; measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), absolute neutrophilcount 1500/ L, plateletcount 75, 000/ L, adequateliverfunction (serum bilirubin level 1.5 mg/dL and aspartate aminotransferase/alanine aminotransferase levels 2.5 times the upper limit ofnormalor 5timestheupperlimitofnormalwithlivermetastases), and serum creatinine level 2.0 mg/dL. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | 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. |
| Primary End Point: | a preliminary evaluation of the efficacy of these 2 high doses |
| Secondary End Point: | evaluation of toxicity |
| Patients Number: | 119 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | n previously untreated patients, the overall response rate was 19%, with a median progression free survival (PFS) of 7.8 months. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS for the entire group was 5.7 months (95% CI, 3.98.6 months). |
| Median OS A vs. C: | Median OS was 18.4 months (95% CI, 13.626.9 months) |
| Adverse Event(agent arm): | 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. |
| Conclusions: | 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 mgkg every 2 weeks. |