Hepatocellular Carcinoma, Hepatoma, Liver Cell Carcinoma, Hepatitis C
Conditions
Keywords
hepatitis C, Elbasvir/grazoprevir, Hepatocellular carcinoma
Brief summary
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) \[EBR/GZR\].
Detailed description
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..
Interventions
Elbasvir / Grazoprevir
Sponsors
Merck Sharp & Dohme LLC
Austin Hospital, Melbourne Australia
Bayside Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Viral eradication | 12 weeks | Eradication of Hepatitis C virus determined by undetectable viral load |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence free survival | 5 years | Recurrence free survival |
| Disease free survival | 5 years | Disease free survival |
| HCC recurrence rate following HCC treatment | 6 and 12 month | impact of DAA therapy on 6 and 12 month HCC recurrence rate following HCC treatment |
| Adverse events | Up to 5 years | Safety and tolerability of Elbasvir/grazoprevir determined by adverse events |
| Time to HCC recurrence / progression | 5 years | Time to HCC recurrence / progression |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Up to 5 years | Overall survival determined by proportion surviving |
Outcome results
None listed