HATCHeT: HepATocellular Cancer Hcv Therapy Study

Sponsor

Bayside Health (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04546802

Collaborator

Merck Sharp & Dohme LLC (Industry), Austin Hospital, Melbourne Australia (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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].

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Hepatoma Liver Cell Carcinoma Hepatitis C	Drug: Elbasvir / Grazoprevir Oral Tablet	Phase 3

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..

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 1, 2019

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Immediate treatment This group will undergo immediate treatment of the HCV once HCC complete response (CR) has been confirmed	Drug: Elbasvir / Grazoprevir Oral Tablet Elbasvir / Grazoprevir
Active Comparator: Delayed treatment This group will delay commencement of the HCV treatment until 6 months after HCC complete response (CR) has been confirmed	Drug: Elbasvir / Grazoprevir Oral Tablet Elbasvir / Grazoprevir

Arm

Intervention/Treatment

Active Comparator: Immediate treatment

This group will undergo immediate treatment of the HCV once HCC complete response (CR) has been confirmed

Drug: Elbasvir / Grazoprevir Oral Tablet

Elbasvir / Grazoprevir

Active Comparator: Delayed treatment

This group will delay commencement of the HCV treatment until 6 months after HCC complete response (CR) has been confirmed

Drug: Elbasvir / Grazoprevir Oral Tablet

Elbasvir / Grazoprevir

Outcome Measures

Primary Outcome Measures

Viral eradication [12 weeks]
Eradication of Hepatitis C virus determined by undetectable viral load

Secondary Outcome Measures

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
Recurrence free survival [5 years]
Recurrence free survival
Disease free survival [5 years]
Disease free survival
Time to HCC recurrence / progression [5 years]
Time to HCC recurrence / progression
Adverse events [Up to 5 years]
Safety and tolerability of Elbasvir/grazoprevir determined by adverse events

Other Outcome Measures

Overall survival [Up to 5 years]
Overall survival determined by proportion surviving

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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