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Trial record 32 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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

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ClinicalTrials.gov Identifier: NCT03110055
Recruitment Status : Unknown
Verified April 2017 by michal roll, Tel-Aviv Sourasky Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : April 12, 2017
Last Update Posted : April 12, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
michal roll, Tel-Aviv Sourasky Medical Center

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.

Condition or disease Intervention/treatment Phase
HCV, HCC Drug: Grazoprevir/Elbasvir Other: Medical records Procedure: Transarterial Chemoembolization Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 1, 2017
Estimated Primary Completion Date : May 1, 2018
Estimated Study Completion Date : May 1, 2019

Arm Intervention/treatment
Experimental: 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.

Drug: Grazoprevir/Elbasvir
anti-viral treatment for HCV

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

Procedure: Transarterial Chemoembolization
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.




Primary Outcome Measures :
  1. Overall survival [ Time Frame: 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

  2. Adverse events and serious adverse events (AEs, SAEs) [ Time Frame: 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

  3. Time to progression (TTP) [ Time Frame: Assessed, up to 24 months ]
    Time from start of treatment until the first documented event of symptomatic progression.

  4. SVR12 rates [ Time Frame: 12 weeks after the last actual dose of Grazoprevir/Elbasvir ]
    : proportion of patients achieving SVR12

  5. Hepatic de-compensation as assessed by clinical end-points [ Time Frame: Once a month up to 24 months ]
    development of ascites, and will undergo repeated liver function tests every 2 weeks to detect CPT increase.


Secondary Outcome Measures :
  1. Time to radiologic progression [ Time Frame: The time from start of treatment to disease progression, according to mRECIST, assessed up to 24 months. ]
    a decrease in tumor in 15 % or more of the patients undergoing combination therapy vs. historical control of TACE alone

  2. Disease-control rate [ Time Frame: at least 28 days after the first demonstration of that rating on the basis of independent radiologic review ]
    The percentage of patients who had a best-response rating of complete response, partial response, or stable disease (according to mRECIST) that was maintained for at least 28 days after the first demonstration of that rating on the basis of independent radiologic review

  3. decrease in tumor markers [ Time Frame: Screening and 24 months. ]
    A 50 % decrease in tumor markers in 15 % or more patients undergoing combination therapy vs. TACE alone

  4. quality of life [ Time Frame: At screening, and months 3,13,22. ]
    Assess quality of life as measured by SF-36 questionnaire

  5. Symptom severity score [ Time Frame: At screening, and months 3,13,22. ]
    Assess severity of symptoms as measured by FSHI8 questionnaire



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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Responsible Party: michal roll, Head of Research and Development department, Principle investigator, MD., Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier: NCT03110055     History of Changes
Other Study ID Numbers: TASMC-16-OS-0702-CTIL
First Posted: April 12, 2017    Key Record Dates
Last Update Posted: April 12, 2017
Last Verified: April 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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MK-5172
Antiviral Agents
Anti-Infective Agents