HepATocellular Cancer Hcv Therapy Study

NCT ID: NCT04546802

Last Updated: 2020-09-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-30
• Study Completion Date: 2023-06-30

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..

Conditions

Hepatocellular Carcinoma; Hepatoma; Liver Cell Carcinoma; Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immediate treatment

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

Group Type: ACTIVE_COMPARATOR

Elbasvir / Grazoprevir Oral Tablet

Intervention Type: DRUG

Elbasvir / Grazoprevir

Delayed treatment

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

Group Type: ACTIVE_COMPARATOR

Elbasvir / Grazoprevir Oral Tablet

Intervention Type: DRUG

Elbasvir / Grazoprevir

Interventions

Elbasvir / Grazoprevir Oral Tablet

Elbasvir / Grazoprevir

Intervention Type: DRUG

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.

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Austin Hospital, Melbourne Australia

OTHER

Sponsor Role: collaborator

Bayside Health

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ms. Rowan Frew

Manager Research and Ethics Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William kemp, MBBSFRACPPhD

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Other Identifiers

288/18

Identifier Type: -

Identifier Source: org_study_id