Y-90 Alone or With Sorafenib for Pre-Transplant Hepatocellular Carcinoma

• To Evaluate sorafenib as an adjunct to Y-90 for control of HCC as a bridge/downstage to transplant [ Time Frame: Up to one year ] [ Designated as safety issue: Yes ]
  Subjects randomized to receive Sorafenib take the drug for 2 weeks before treatment with Y90. They have imaing (CT/MRI) 2 weeks after starting Sorafenib then are treated. Post-treatment patients have blood drawn and adverse event evaluation at 2 weeks, 4 weeks, 6 weeks, and then every 6 weeks up to 1 year or time of transplant. Repeat imaging is done at 4 weeks, and then every 3 months post-treatment. Subjects not receiving Sorafenib are terated with Y90 and then are evaluated post-treatment the same as the subjects that receive the drug.
  
  

• To characterize the toxicity profile of sorafenib and Y90 using NCI CTC toxicity grading scales. [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
  Subjects randomized to receive Sorafenib take the drug for 2 weeks before treatment with Y90. They have imaing (CT/MRI) 2 weeks after starting Sorafenib then are treated. Post-treatment patients have blood drawn and adverse event evaluation at 2 weeks, 4 weeks, 6 weeks, and then every 6 weeks up to 1 year or time of transplant. Repeat imaging is done at 4 weeks, and then every 3 months post-treatment. Subjects not receiving Sorafenib are terated with Y90 and then are evaluated post-treatment the same as the subjects that receive the drug.
  
  
• To identify predictive and prognostic markers of how the liver cancer will respond to treatment. [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
  All subjects are evaluated with lab work and adverse event assessment at 2, 4, and 6 weeks post-treatment, and then every 6 weeks up to 1 year or when they receive tranplant.
  
  

Because Hepatocellular carcinoma (HCC) grows by forming new blood vessels liver transplant (OLT) offers the best chance for long term survival. However, with the growing number of patients who require OLT, prolonged wait list times often lead to drop out from the transplant list due to tumor progression. Some patients are granted an "upgrade",within the generally accepted guidelines for transplant eligibility, in order to expedite the access of patients with early HCC to transplantation before tumor progression. The use of therapies like radioembolization also known as Yttrium-90 ([Y-90] a procedure where very small beads coated with radiation are injected directly into the tumor through an artery in your groin) while awaiting OLT has become common at most transplant centers, including Northwestern, to help patients reach transplant. Additionally, these treatments are being used to move patients to a status eligible for transplant. We are studying whether a combination approach with systemic therapy and therapy applied directly to the liver, will be more successful than a single therapy . Angiogenesis (a process involving the growth of new blood vessels from pre-existing vessels) plays an important role in the early stages of HCC. A decrease in angiogenesis both locally within the treated tumor as well as in any existing tumor cells, not yet detected, would hopefully decrease the incidence of post transplant recurrence of HCC. All subjects enrolled in this study will be treated with the use of Therasphere, Y-90, which is composed of nonbiodegradable glass microspheres coated with the radioactive compound Y-90 which are injected into the hepatic artery. The concentrated radioactive microspheres within the tumor lead to "inside-out" radiation. Half of the subjects will be treated with sorafenib (NEXAVAR®) in conjunction with Y-90. The determination of which subjects will receive sorafenib will be made randomly, like the flip of a coin. Sorafenib works by slowing the growth of the tumor cell , attacking the tumor from the outside. Researchers hope to determine whether the subjects treated with sorafenib have an overall improved response to liver directed therapy with Y-90 Therasphere.