Phase I trial of sorafenib in high-risk hepatocellular carcinoma (HCC) patients after liver transplantation (LT).

Abstract

TPS211 Background: Liver transplantation offers long-term survival for 75-80% of HCC patients who fall within the Milan criteria. For those who fall outside these criteria, rates of recurrence are much higher. About a third of HCC patients are transplanted outside Milan criteria at our institution. There are no known treatments that decrease risk of recurrence post-transplant. Sorafenib is a tyrosine kinase inhibitor which targets several pathways, including VEGFR2-3, PDGFR and Raf. It was the first drug approved for the treatment of advanced HCC in the United States. We began a phase I dose escalation study of sorafenib in high-risk HCC patients after liver transplantation at our center to assess safety in preparation for a larger study to evaluate efficacy in this population. Methods: Eligible subjects include patients with biopsy-proven HCC outside Milan criteria, those with poorly differentiated tumors, or with microvascular invasion at explant. We are using a standard phase I dose-escalation design, beginning drug between 4 and 12 weeks after liver transplantation, with a planned duration of treatment of 6 months. Cohort dosages are as follows: 1) 200 mg q day, 2) 200 mg BID, 3) 200 mg/400 mg, and 4) 400 mg BID. Correlative studies include circulating endothelial cells (CECs) and plasma angiogenic and inflammatory markers which are being collected prior to treatment, at 1 month, and at recurrence in a subset of patients as possible predictive and prognostic biomarkers. CECs are assayed by mixing whole blood with a ferrofluid of magnetic nanoparticles coated with antibodies to CD146, which captures endothelial cells. Cells are then stained with CD105, CD45, and the nuclear stain DAPI. CECs are identified as CD105(+), DAPI(+), and CD45(-). Plasma markers include VEGF, VEGFR2, and IL- 6. We have enrolled 4 patients out of a planned enrollment of 24 patients. We are planning a larger phase II feasibility study though the Southwest Oncology Group (SWOG). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Investigator's Meeting Research project