Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular Carcinoma, TACE, Durvalumab, Bevacizumab, Liver Cancer
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
Interventions
DRUGDurvalumab
Durvalumab IV (intravenous)
DRUGBevacizumab
Bevacizumab IV (intravenous)
OTHERPlacebo
Saline solution for Durvalumab and/or Bevacizumab masking (IV intravenous)
TACE (chemo and embolic agent injection into the hepatic artery)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) for Arm B vs Arm C | Approximately 5 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 5 years | OS is defined as the time from the date of randomization until death due to any cause |
| Progression Free Survival (PFS) for Arm A vs Arm C | Approximately 5 years | 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 |
| 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) | Approximately 5 years | Collection of patient reported outcome (PRO) measures to assess time to deterioration in global health status/quality of life (QoL), functioning (physical) and symptoms |
| 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) | Approximately 5 years | Collection of patient reported outcome (PRO) measures to assess time to deterioration in symptoms |
Other
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) of Durvalumab and Bevacizumab as determined by peak serum concentrations | Approximately 5 years |
| Immunogenicity of Durvalumab and Bevacizumab as measured by presence of anti-drug antibodies (ADAs) | Approximately 5 years |
| Safety of Durvalumab and Bevacizumab as evaluated by summary of adverse events by treatment arm and CTCAE grade | Approximately 5 years |
Countries
Australia, Brazil, Canada, China, France, Hong Kong, India, Italy, Japan, Mexico, Russia, Singapore, South Korea, Spain, Taiwan, Thailand, United States, Vietnam
Outcome results
None listed