1. Phase I Trial of Sorafenib in High-Risk Hepatocellular Carcinoma (HCC) Patients After Liver Transplantation (LT) AB Siegel, R Hidalgo, D Tsushima, J Zaretsky, K Halazun, I Matushansky, J Emond, RS Brown Jr, T Kato Columbia University College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, and Center for Liver Disease and Transplantation, New York, NY

2. Introduction LT offers long-term survival for HCC patients who fall within the Milan criteria (1 tumor ≤5 cm, ≤3 tumors, each ≤3 cm, and no gross vascular invasion on preoperative imaging For those who fall outside these criteria, rates of recurrence are much higher. About a third of patients with HCC are transplanted outside Milan criteria at our institution We began a Phase I dose escalation study of sorafenib in high-risk patients with HCC after liver transplantation at our center to assess safety in preparation for a larger study to evaluate efficacy in this population Adapted from Siegel AB et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

3. Study Design We have enrolled 7 out of a planned 24 patients. 1 Patient in the first cohort had a DLT (increased GGT) The first patient in the second cohort was dose-reduced from 200 mg BID to 200 mg QD Liver Transplant 4-12 weeks after transplant Sorafenib dose escalation cohorts: 1. 200 mg QD 2. 200 mg BID 3. 200 mg / 400 mg 4. 400 mg BID Patients: Biopsy-proven HCC that was 1) outside Milan criteria (pre- or posttransplant), 2) poorly differentiated pathology, or 3) had vascular invasion at explant. DLT=dose-limiting toxicity; GGT=gamma-glutamyltransferase. Adapted from Siegel AB et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

4. Methods Correlative studies include circulating endothelial cells (CECs) and plasma angiogenic and inflammatory markers that are being collected prior to treatment, at 1 month, and at recurrence in a subset of patients as possible predictive and prognostic biomarkers Adapted from Siegel AB et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

5. CEC Assay CECs are assayed by mixing whole blood with a ferrofluid of magnetic nanoparticles coated with antibodies to CD 146, which captures endothelial cells. Cells are then stained with CD105, CD45, and the nuclear stain DAPI. CECs are identified as CD105 (+), DAPI (+), and CD45 (-) Adapted from Siegel AB et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.

6. Conclusions A post-transplant HCC study for high-risk patients is feasible Accrual barriers at our site include postoperative illness and disenfranchised population Expansion to UCLA and USC is underway to improve accrual We will present toxicity and recurrence data next year; average follow-up is now more than a year Adapted from Siegel AB et al. Presented at: ASCO Annual Meeting; June 3-7, 2011; Chicago, IL.