the Effect of Grazoprevir/Elbasvir and TACE vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated HCC.

Pilot Study to Assess the Effect of Grazoprevir/Elbasvir (ZEPATIER™) and Transarterial Chemoembolization (TACE) vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths in the world. Hepatitis C virus (HCV) is the most common underlying cause of cirrhosis and HCC in the western world. Most patients with HCC present with either non-resectable tumor and/or severe underlying liver dysfunction, and are not suitable candidates for curative treatments by resection or transplantation. Thus, for the majority of patients with HCV related HCC, the only option is prolongation of life without a chance for cure. These patients generally have a poor prognosis with a median survival of less than 1 year. Arterial obstruction of branches of the hepatic artery and simultaneous infusion of chemotherapy (Trans-arterial chemo-embolization or TACE) induces ischemic tumor necrosis with a high rate of objective tumor responses (30-60%). Overall, the median survival after TACE for intermediate HCC is about 20 months, an improvement over supportive care. Treatment with Grazoprevir/Elbasvir showed excellent results in phase 3 studies for patients with HCV genotype 1 (a and b) and genotype 4 infection and is approved for HCV treatment in the USA, Europe and Israel. Anti-HCV therapies may influence HCC biology by decreasing inflammation and may thus alter the tumor microenvironment.

Single center, open label, prospective pilot study. The study will include 20 HCV genotype 1 (a and b) cirrhotic patients (Child Pugh A compensated cirrhosis) with advanced, un-resectable HCC who are eligible for TACE. This pilot study will have one arm which will be compared to historical controls. All patients participating in the study will receive Grazoprevir/Elbasvir treatment according to established guidelines together with regular TACE treatments. The historical controls will refer to patients who received regular TACE treatments alone (standard of HCC care). Follow up will be for up to 24 months from TACE initiation.

Inclusion Criteria:

1. Patients with chronic HCV genotype 1 (a and b) infection and un-resectable HCC who are eligible for TACE
2. Ages 18-75 years
3. Willing to take part in a clinical trial and have signed an informed consent
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
5. Child-Pugh liver function class A
6. Patients with expected survival of less than 1 year
7. Adequate hematologic function (plt≥60, 000 /L; Hb≥8.5 g/dl; and INR≤1.7
8. Adequate hepatic function (albumin ≥3.5 g/dl; total bilirubin, ≤2 mg/dl; ALT and AST ≤5 times the upper limit of the normal range)
9. Adequate renal function (serum creatinine ≤1.5 times the upper limit of normal range).

Exclusion Criteria:

1. Patients unwilling to sign the informed consent
2. Patients unwilling or not capable to complete the anti-viral treatment with Grazoprevir/Elbasvir
3. CPT score >7
4. Patients ineligible for TACE
5. Patients with contraindications to elbasvir/grazoprevir
6. Patients suffering from other underlying liver disease (HBV, HIV, PSC, PBC, AIH etc.)
7. Patients with malignancies other than HCC
8. Patients with previous anti-HCC treatment (RFA, TACE, SIRT or sorafenib)
9. Active alcohol or substance use
10. Previous liver transplantations
11. Child Pugh B or C cirrhosis
12. Total serum bilirubin >1.9 mg/dL
13. Extra-hepatic spread (metastases)
14. Pregnant/lactating women, minors and disabled/incapacitated persons