Entry Detail
| General information | |
| Database: | DB00112 |
| Objective: | To determine the clinical and biologic effects of bevacizumab, an antivascular endothelial growth factor (VEGF) monoclonal antibody, in unresectable hepatocellular carcinoma (hepatocellular carcinoma). |
| Authors: | Siegel AB, et al |
| Title: | Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2008 |
| PMID: | 18565886 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab |
| Target: | Vascular endothelial growth factor Epidermal growth factor receptor |
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II Study |
| Key Patients Feature: | Adults with organconfined hepatocellular carcinoma, Eastern Cooperative Oncology Group performance status of 0 to 2, and compensated liver disease |
| Biomarker: | circulating VEGFA and stromalderived factor1 (SDF1) |
| Biomark Analysis: | Bevacizumab was associated with reductions in circulating VEGFA and stromalderived factor1 levels. Functional angiogenic activity was associated with VEGFA levels in patient plasma. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received bevacizumab 5 mg/kg (n = 12) or 10 mg/kg (n = 34) every 2 weeks until disease progression or treatmentlimiting toxicity. |
| Primary End Point: | whether bevacizumab improved the 6month PFS from 40% to 60%. |
| Secondary End Point: | the effects of bevacizumab on arterial enhancement and on plasma cytokine levels and the capacity of patients' plasma to support angiogenesis via an in vitro assay. |
| Patients Number: | 46 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 13%; 95% CI, 3% to 23%, |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 65% were progression free at 6 months, median PFS time was 6.9 months (95% CI, 6.5 to 9.1 months); |
| Median OS A vs. C: | overall survival rate was 53% at 1 year, 28% at 2 years, and 23% at 3 years. |
| Adverse Event(agent arm): | Grade 3 to 4 adverse events included hypertension (15%) and thrombosis (6%, including 4% with arterial thrombosis). Grade 3 or higher hemorrhage occurred in 11% of patients, including one fatal variceal bleed. |
| Conclusions: | they observed significant clinical and biologic activity for bevacizumab in nonmetastatic hepatocellular carcinoma and achieved the primary study end point. Serious bleeding complications occurred in 11% of patients. Further evaluation is warranted in carefully selected patients. |