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
试验速览
- 阶段
- 不适用
- 入组人数
- 20
- 主要终点
- Time to progression (TTP)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with chronic HCV genotype 1 (a and b) infection and un-resectable HCC who are eligible for TACE
- •Ages 18-75 years
- •Willing to take part in a clinical trial and have signed an informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
- •Child-Pugh liver function class A
- •Patients with expected survival of less than 1 year
- •Adequate hematologic function (plt≥60, 000 /L; Hb≥8.5 g/dl; and INR≤1.7
- •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)
- •Adequate renal function (serum creatinine ≤1.5 times the upper limit of normal range).
排除标准
- •Patients unwilling to sign the informed consent
- •Patients unwilling or not capable to complete the anti-viral treatment with Grazoprevir/Elbasvir
- •CPT score >7
- •Patients ineligible for TACE
- •Patients with contraindications to elbasvir/grazoprevir
- •Patients suffering from other underlying liver disease (HBV, HIV, PSC, PBC, AIH etc.)
- •Patients with malignancies other than HCC
- •Patients with previous anti-HCC treatment (RFA, TACE, SIRT or sorafenib)
- •Active alcohol or substance use
- •Previous liver transplantations
- •Child Pugh B or C cirrhosis
- •Total serum bilirubin >1.9 mg/dL
- •Extra-hepatic spread (metastases)
- •Pregnant/lactating women, minors and disabled/incapacitated persons
研究组 & 干预措施
HCV patients with un-resectable HCC
HCV genotype 1 (a and b) cirrhotic patients (child pugh A compensated cirrhosis) with advanced and un-resectable HCC who are eligible for TACE . The patients will receive Grazoprevir/Elbasvir and Transarterial Chemoembolization.
Their outcomes will be compared to the medical records of patients who underwent Transarterial Chemoembolization only, in the past.
干预措施: Grazoprevir/Elbasvir (Drug)
HCV patients with un-resectable HCC
HCV genotype 1 (a and b) cirrhotic patients (child pugh A compensated cirrhosis) with advanced and un-resectable HCC who are eligible for TACE . The patients will receive Grazoprevir/Elbasvir and Transarterial Chemoembolization.
Their outcomes will be compared to the medical records of patients who underwent Transarterial Chemoembolization only, in the past.
干预措施: Medical records (Other)
HCV patients with un-resectable HCC
HCV genotype 1 (a and b) cirrhotic patients (child pugh A compensated cirrhosis) with advanced and un-resectable HCC who are eligible for TACE . The patients will receive Grazoprevir/Elbasvir and Transarterial Chemoembolization.
Their outcomes will be compared to the medical records of patients who underwent Transarterial Chemoembolization only, in the past.
干预措施: Transarterial Chemoembolization (Procedure)
结局指标
主要结局
Time to progression (TTP)
时间窗: Assessed, up to 24 months
Time from start of treatment until the first documented event of symptomatic progression.
Overall survival
时间窗: assessed up to 24 months
15% or more increase in survival with the combination treatment of Grazoprevir/Elbasvir and TACE vs. historical control of TACE alone; Time Frame: from start of treatment to death from any cause, or last known date of survival
SVR12 rates
时间窗: 12 weeks after the last actual dose of Grazoprevir/Elbasvir
: proportion of patients achieving SVR12
Adverse events and serious adverse events (AEs, SAEs)
时间窗: 24 months
will be assessed in all patients receiving at least one dose of a combination therapy, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Hepatic de-compensation as assessed by clinical end-points
时间窗: Once a month up to 24 months
development of ascites, and will undergo repeated liver function tests every 2 weeks to detect CPT increase.
次要结局
- Symptom severity score(At screening, and months 3,13,22.)
- quality of life(At screening, and months 3,13,22.)
- Disease-control rate(at least 28 days after the first demonstration of that rating on the basis of independent radiologic review)
- Time to radiologic progression(The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months.)
- decrease in tumor markers(Screening and 24 months.)
研究者
michal roll
Head of Research and Development department, Principle investigator, MD.
Tel-Aviv Sourasky Medical Center