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

NCT03110055 | Unknown

• 1 other identifier: TASMC-16-OS-0702-CTIL
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HCV, HCC

Outcome Measures

Primary Outcomes (5)

• Overall survival

  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

  assessed up to 24 months

• Adverse events and serious adverse events (AEs, SAEs)

  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

  24 months

• Time to progression (TTP)

  Time from start of treatment until the first documented event of symptomatic progression.

  Assessed, up to 24 months

• SVR12 rates

  : proportion of patients achieving SVR12

  12 weeks after the last actual dose of Grazoprevir/Elbasvir

• Hepatic de-compensation as assessed by clinical end-points

  development of ascites, and will undergo repeated liver function tests every 2 weeks to detect CPT increase.

  Once a month up to 24 months

Secondary Outcomes (5)

• Time to radiologic progression

  The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months.

• Disease-control rate

  at least 28 days after the first demonstration of that rating on the basis of independent radiologic review

• decrease in tumor markers

  Screening and 24 months.

• quality of life

  At screening, and months 3,13,22.

• Symptom severity score

  At screening, and months 3,13,22.

Study Arms (1)

HCV patients with un-resectable HCC

EXPERIMENTAL

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.

Drug: Grazoprevir/Elbasvir; Other: Medical records; Procedure: Transarterial Chemoembolization

Interventions

Grazoprevir/Elbasvir DRUG

anti-viral treatment for HCV

HCV patients with un-resectable HCC

Medical records OTHER

Medical records of patients who underwent Transarterial Chemoembolization only, in the past.

HCV patients with un-resectable HCC

Transarterial Chemoembolization PROCEDURE

A minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.

HCV patients with un-resectable HCC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Hepatitis C

Interventions

elbasvir-grazoprevir drug combination; Medical Records

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Records; Data Collection; Epidemiologic Methods; Investigative Techniques; Organization and Administration; Health Services Administration; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Research and Development department, Principle investigator, MD.

Model Details: 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.

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: April 12, 2017
• Study Start: May 1, 2017
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2019
• Last Updated: April 12, 2017

Record last verified: 2017-04