Entry Detail
| General information | |
| Database: | DB00931 |
| Objective: | Thisphase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (hepatocellular carcinoma) patients. |
| Authors: | AbouAlfa GK, et al |
| Title: | Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 16908937 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II study |
| Key Patients Feature: | Patients with inoperable hepatocellular carcinoma, no prior systemic treatment, and ChildPugh (CP) A or B |
| Biomarker: | phosphorylated extracellular signal regulated kinase (pERK) in pretreatment biopsies (immunohistochemistry) and bloodcell RNA expression patterns in selected patients |
| Biomark Analysis: | There were no significant pharmacokinetic differences between CP A and B patients. Pretreatment tumor pERK levels correlated with TTP. |
| Control Group Info: | single arm |
| Treatment Info: | pts received continuous, oral sorafenib 400 mg bid in 4week cycles |
| Primary End Point: | efficacy, toxicity, pharmacokinetics, and biomarkers |
| Secondary End Point: | NA |
| Patients Number: | 137 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 8% |
| Disease Control Rate: | 41.60% |
| Median Time to Progression: | 4.2 months |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 9.2 months |
| Adverse Event(agent arm): | The most common drugrelated adverse events (any grade) were dermatologic, constitutional, and GI (Table 5). Grade 3 toxicities included fatigue (9.5%), diarrhea (8.0%), and HFS (5.1%). |
| Conclusions: | Although singleagent sorafenib has modest efficacy in hepatocellular carcinoma, the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents. |