Clinical trial NCT03110055: the Effect of Grazoprevir/Elbasvir and TACE vs. TACE Alone in Prolonging Survival of Patients With Non-resectable HCV Associated HCC.
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HCV, HCC
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-04-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single center, open label, prospective pilot study. The study will enroll 20 HCV genotype 1 cirrhotic patients with advanced and un-resectable HCC who are eligible for TACE. The patients will receive Grazoprevir/Elbasvir anti-viral treatment in accordance with established guidelines together with regular TACE treatments. Follow up will be for up to 24 months from TACE initiation.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: assessed up to 24 months
measure: Adverse events and serious adverse events (AEs, SAEs)
timeFrame: 24 months
measure: Time to progression (TTP)
timeFrame: Assessed, up to 24 months
measure: SVR12 rates
timeFrame: 12 weeks after the last actual dose of Grazoprevir/Elbasvir
measure: Hepatic de-compensation as assessed by clinical end-points
timeFrame: Once a month up to 24 months
Secondary outcomes:
measure: Time to radiologic progression
timeFrame: The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months.
measure: Disease-control rate
timeFrame: at least 28 days after the first demonstration of that rating on the basis of independent radiologic review
measure: decrease in tumor markers
timeFrame: Screening and 24 months.
measure: quality of life
timeFrame: At screening, and months 3,13,22.
measure: Symptom severity score
timeFrame: At screening, and months 3,13,22.
Other outcomes:
Locations:
Study officials:
References: