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Recruitment will be too difficult due to available PBS funded treatment and recent Australian clinical guidelines will conflict with the premise of the study.
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Austin Hospital, Melbourne Australia | OTHER |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immediate treatment | Active Comparator | This group will undergo immediate treatment of the HCV once HCC complete response (CR) has been confirmed |
|
| Delayed treatment | Active Comparator | This group will delay commencement of the HCV treatment until 6 months after HCC complete response (CR) has been confirmed |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Elbasvir / Grazoprevir Oral Tablet | Drug | Elbasvir / Grazoprevir |
|
| Measure | Description | Time Frame |
|---|---|---|
| Viral eradication | Eradication of Hepatitis C virus determined by undetectable viral load | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| HCC recurrence rate following HCC treatment | impact of DAA therapy on 6 and 12 month HCC recurrence rate following HCC treatment | 6 and 12 month |
| Recurrence free survival | Recurrence free survival |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | Overall survival determined by proportion surviving | Up to 5 years |
Inclusion Criteria:
Exclusion Criteria:
Enrolment in other investigation / experimental therapies
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:
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| Name | Affiliation | Role |
|---|---|---|
| William kemp, MBBSFRACPPhD | The Alfred | Principal Investigator |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000611265 | elbasvir-grazoprevir drug combination |
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| 5 years |
| Disease free survival | Disease free survival | 5 years |
| Time to HCC recurrence / progression | Time to HCC recurrence / progression | 5 years |
| Adverse events | Safety and tolerability of Elbasvir/grazoprevir determined by adverse events | Up to 5 years |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |