Pilot Study: Safety and Feasibility of Using Sorafenib as Neoadjuvant Treatment Prior to Orthotopic Liver Transplantation (OLT) in Patients With Hepatocellular Carcinoma
• To evaluate safety (including possible surgical complication) and feasibility of using
sorafenib as neo-adjuvant (bridging therapy) prior to orthotopic liver transplant(OLT).
The primary goal of this pilot study is to assess the safety and feasibility of treating
HCC patients with sorafenib prior to OLT, as determined by the number of patients
experiencing grade 4 hemorrhaging or bleeding post-operatively.
To achieve these goals a 2-stage accrual design will be used with a maximum accrual goal of
10 patients. Initially 5 patients will be entered on-study. If more than one patient
experiences grade 4 hemorrhaging/bleeding following OLT the trial will be closed and
sorafenib will not be considered safe and/or feasible. If no patient experiences this event
5 additional patients will be enrolled. At the end of the study sorafenib will be considered
safe and feasible in this setting if no patient experience grade 4 hemorrhaging/bleeding
following transplant. With this design, and assuming at least 3 of the 5 patients in each
cohort undergo OLT, the likelihood of stopping early is <.04 if the underlying risk
hemorrhages/bleeding are low (<5% each) whereas there is a >.42 chance of early termination
if the risks are substantial (e.g. >.20 likelihood of dose limiting toxicity and >.30
likelihood of >grade 4 hemorrhages/bleeding). Overall the likelihood of accepting or not
accepting sorafenib as safe and feasible are >.84, and <.16, respectively under these
- Drop out rate
- Time to progression prior to orthotopic liver transplant (OLT)
- Waiting time.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Adverse events associated with technical aspects of the operation
To assess the safety and feasibility of treating HCC patients with sorafenib prior to OLT, as determined by the number of patients experiencing grade 4 hemorrhaging needing blood trnasfusion, thrombosis of vascular graft structures, stenosis of vascular anastomosis or biliary leaks or anastomotic biliary stenosis.
Robert Pelley, MD
CCF Taussig Cancer Solid Tumor Oncology
United States: Institutional Review Board
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|