| General information |
| Database: | DB00123 |
| Objective: | The MET receptor is dysregulated in hepatocellular carcinoma (hepatocellular carcinoma), thisphase1b study assessed tivantinib safety as primary objective in patients with previously treated hepatocellular carcinoma and ChildPugh A or B liver cirrhosis. |
| Authors: | Santoro A, et al |
| Title: | a phase1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis |
| Journal: | Br J Cancer. |
| Year: | 2013 |
| PMID: | 23287988 |
| Trial Design |
| Clinical Trial Id: | NCT00802555 |
| Agent: | tivantinib
|
| Target: | Protooncogene cMet
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I, openlabel, singlearm study |
| Key Patients Feature: | histologically or cytologically confirmed advanced hepatocellular carcinoma, Barcelona Clinic Liver Cancer (BCLC) stage A-C (Forner et al, 2012), and ChildPugh A cirrhosis with no clinical ascites |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity. |
| Primary End Point: | The primary objective was safety, with the goal of defining the RP2D in cirrhotic hepatocellular carcinoma patients. |
| Secondary End Point: | TTP, objective response rate, disease control rate, and tivantinib pharmacokinetics. |
| Patients Number: | 21 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). |
| Median Time to Progression: | 3.3 months |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | common drugrelated AEs were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drugrelated worsening of liver function or performance status occurred, but one ChildPugh B patient experienced drugrelated bilirubin increase. Four patients had drugrelated serious AEs, including one neutropaeniarelated death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. |
| Conclusions: | Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with hepatocellular carcinoma and ChildPugh A or B cirrhosis. |