HepATocellular Cancer Hcv Therapy Study
HepATocellular Cancer Hcv Therapy Study
Subjects with Hepatitis C Virus (HCV) infection, genotype 1 or 4 and with hepatocellular
 carcinoma (HCC) and a complete response to HCC therapy will be randomised to immediate or
 delayed (6 months) HCV therapy with Elbasvir (MK-8742) and Grazoprevir (MK-5172) [EBR/GZR].
Two cohorts (A and B) of patients with chronic HCV infection will be enrolled. Patients will
 be eligible for enrollment if they fulfill the study inclusion and exclusion criteria and
 have achieved a complete tumour response (CR) 3 months (+/- 14 days) following HCC treatment

 -  Cohort A: Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who have
 received curative therapy defined as either; liver transplantation, surgical resection
 or local ablation with curative intent and attained a radiologically confirmed CR.
 (N=50)

 -  Cohort B: Patients who are non-eligible for curative therapy but have attained a
 radiologically confirmed CR. post embolization or ablative therapy and have chronic HCV
 infection. (N=50) Given the existing uncertainty regarding the impact of direct acting
 antiviral (DAA) therapy on HCC recurrence, study participants will be randomized to
 receive DAA treatment as "immediate" ie upon study enrollment or "delayed" ie treatment
 commenced ≥ 6months following documentation of complete response based on radiological
 assessment indicating no residual arterial enhancing disease..
Inclusion Criteria:

 -  Hepatitis C diagnosed as the HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time
 of screening

 -  Genotype inclusions

 -  Have documented chronic HCV GT1 or GT4, (with no evidence of nontypeable or mixed
 genotype) infection

 -  HCC diagnosed on the basis of histology or according to AASLD radiological criteria,

 -  Written informed consent granted prior to initiation of any study-specific screening
 procedures

 -  Patients aged 18 to 70 years-old;

 -  Child-Pugh ≤≤ A6

 -  BCLC stage 0, A HCC or no detectable HCC in a patient who has undergone a curative
 form of treatment (liver transplantation, surgical resection of local ablative therapy
 with curative intent) OR BCLC-B disease but clinically stable with non-evidence of
 disease progression as demonstrated by either Triphasic CT or contrast MRI at least 3
 months after the last HCC treatment.

 Exclusion Criteria:

 -  Enrolment in other investigation / experimental therapies

 -  Prior or current use of Sorafenib or other systemic chemotherapy

 -  Life expectancy < 12 months (unless transplantation eligible)

 -  Unable to provide informed consent

 -  Previous or concurrent cancer that is distinct from HCC in primary site or
 histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and
 superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3
 years prior to enrollment is permitted.

 -  Any condition that in the opinion of the investigator would impair participation in
 the trial.

 -  Coinfected with human immunodeficiency virus (HIV) infection or Hepatitis B virus
 (e.g. HBsAg positive).

 -  History of congestive heart failure defined as Class II to IV per New York Heart
 Association (NYHA) classification within 6 months prior to study entry; active
 coronary artery disease (CAD); clinically significant bradycardia or other
 uncontrolled, cardiac arrhythmia defined as ≥ Grade 3 according to National Cancer
 Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03,
 or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to
 study entry (myocardial infarction occurring > 6 months prior to study entry is
 permitted)

 -  Active clinically serious infections defined as ≥ Grade 3 according to NCI CTCAE,
 version 4.03 6. Any medical, psychological, or social conditions, particularly if
 unstable, including substance abuse, that may, in the opinion of the Investigator,
 interfere with the subject's safety or participation in the study, protocol
 compliance, or evaluation of the study results

 -  Concomitant interferon therapy or therapies for active Hepatitis C Virus (HCV)
 infection. Prior interferon and/or ribavirin therapy is not a contraindication to
 enrolment however previous treatment with direct acting antiviral treatment is an
 exclusion

 -  Pregnancy or breast-feeding

 -  Inability to swallow oral medications

 -  Clinically significant gastrointestinal bleeding occurring ≤ 3 months prior to study
 entry or Large gastric-esophageal varices (larger than 5 cm) or previous history of
 gastric-esophageal bleeding due to varices.

 -  Fulfills exclusion criteria on biochemistry results:

 -  Creatinine Clearance <50 mL/min

 -  Hemoglobin <11 g/dL for females and <12 g/dL for males

 -  Platelets <75 x 103/μL

 -  Serum Albumin < 3.0 g/dL

 -  INR >1.7

 -  HbA1c >10%

 -  ALT >10XULN, AST >10XULNtherapy