Clinical trial NCT04546802: HepATocellular Cancer Hcv Therapy Study
Official title: Open Label Trial to Study the Efficacy and Safety of MK-5172 and MK-8742 +/- Ribavirin (RBV) in the Treatment of Hepatitis C G1 and 4, in Patients Eligible for Liver Transplant (HCC) or Curative Therapy or Clinically Stable Disease Post Local Resection, Embolization or Ablative Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Hepatoma
Liver Cell Carcinoma
Hepatitis C
Keywords: hepatitis C
Elbasvir/grazoprevir
Hepatocellular carcinoma
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
name: Austin Hospital, Melbourne Australia
First posted: 2020-09-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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..

Eligibility criteria: 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

Primary outcomes:
measure: Viral eradication
timeFrame: 12 weeks
Secondary outcomes:
measure: HCC recurrence rate following HCC treatment
timeFrame: 6 and 12 month
measure: Recurrence free survival
timeFrame: 5 years
measure: Disease free survival
timeFrame: 5 years
measure: Time to HCC recurrence / progression
timeFrame: 5 years
measure: Adverse events
timeFrame: Up to 5 years
Other outcomes:
measure: Overall survival
timeFrame: Up to 5 years
Locations:
Study officials:
affiliation: The Alfred
name: William kemp, MBBSFRACPPhD
role: PRINCIPAL_INVESTIGATOR
References: