A Global Study to Evaluate Transarterial Chemoembolization (TACE) in Combination With Durvalumab and Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
A global study to evaluate transarterial chemoembolization (TACE) in combination with durvalumab and bevacizumab therapy in patients with locoregional hepatocellular carcinoma

Detailed Description
-----------------
This is a randomized, double-blind, placebo-controlled, multicenter, global Phase III study to determine the efficacy and safety of transarterial chemoembolization (TACE) treatment in combination with durvalumab monotherapy or TACE given with durvalumab plus bevacizumab therapy compared to TACE therapy alone in patients with locoregional hepatocellular carcinoma not amenable to curative therapy

Official Title
-----------------
A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Transarterial Chemoembolization (TACE) in Combination With Either Durvalumab Monotherapy or Durvalumab Plus Bevacizumab Therapy in Patients With Locoregional Hepatocellular Carcinoma (EMERALD-1)

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: Durvalumab
* Drug: Bevacizumab
* Other: Placebo
* Procedure: Transarterial Chemoembolization (TACE)


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: No evidence of extrahepatic disease Disease not amenable to curative surgery or transplantation or curative ablation but disease amenable to TACE Child-Pugh score class A to B7 and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment Measurable disease by Modified Response Criteria in Solid Tumors (mRECIST) criteria Adequate organ and marrow function Key Exclusion Criteria Any history of nephrotic or nephritic syndrome Clinically significant cardiovascular disease or history of arterioembolic event including a stroke or myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within 6 months prior to randomization Any prior or current evidence of coagulopathy or bleeding diathesis or patients who had any kind of surgery in the past 28 days (biopsies are exempt from this exclusion) History of abdominal fistula or GI perforation, non healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment Patients with Vp3 and Vp4 portal vein thrombosis on baseline imaging are excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Transarterial Chemoembolization (TACE) in combination with Durvalumab | Drug: Durvalumab<br>* Durvalumab IV (intravenous)<br>* Other names: MEDI4736;Other: Placebo<br>* Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous)<br>Procedure: Transarterial Chemoembolization (TACE)<br>* TACE (chemo and embolic agent injection into the hepatic artery)<br>|
| Experimental: Arm B<br>Transarterial Chemoembolization (TACE) in combination with Durvalumab and Bevacizumab | Drug: Durvalumab<br>* Durvalumab IV (intravenous)<br>* Other names: MEDI4736;Drug: Bevacizumab<br>* Bevacizumab IV (intravenous)<br>* Other names: AVASTIN;Procedure: Transarterial Chemoembolization (TACE)<br>* TACE (chemo and embolic agent injection into the hepatic artery)<br>|
| Placebo Comparator: Arm C<br>Transarterial Chemoembolization (TACE) in combination with Placebos | Other: Placebo<br>* Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous)<br>Procedure: Transarterial Chemoembolization (TACE)<br>* TACE (chemo and embolic agent injection into the hepatic artery)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) for Arm B vs Arm C | PFS per Blinded Independent Central Review (BICR) assessment will be defined as the time from the date of randomization until the date of first objective disease progression or death | Approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) for Arm A vs Arm C | PFS per Blinded Independent Central Review (BICR) assessment will be defined as the time from the date of randomization until the date of first objective disease progression or death | Approximately 5 years | 
| Overall Survival (OS) | OS is defined as the time from the date of randomization until death due to any cause | Approximately 5 years | 
| Health status/quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30) | Collection of patient reported outcome (PRO) measures to assess time to deterioration in global health status/quality of life (QoL), functioning (physical) and symptoms | Approximately 5 years | 
| Disease-related symptoms measured by European Organization for Research and Treatment of Cancer (EORTC) 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) | Collection of patient reported outcome (PRO) measures to assess time to deterioration in symptoms | Approximately 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatocellular Carcinoma, TACE, Durvalumab, Bevacizumab, Liver Cancer