Hepatocellular Carcinoma
Conditions
Brief summary
This study will evaluate the efficacy and safety of atezolizumab plus bevacizumab combined with on-demand TACE compared to on-demand TACE alone in participants with hepatocellular carcinoma who are at high risk of poorer outcome following TACE treatment.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until participant experience loss of clinical benefit as evaluated by the investigator or unacceptable toxicity or withdrawal of informed consent.
DRUGBecavizumab
Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle.
TACE will be performed by clinical demand.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of HCC by histology/ cytology or clinical criteria * Eligible for TACE treatment * No prior systemic therapy for HCC, especially immunotherapy * No prior locoregional therapy to the target lesion(s) * At least one measurable untreated lesion * ECOG Performance Status of 0-1 * Child-Pugh class A
Exclusion criteria
* Evidence of Vp3/4 and hepatic vein tumor thrombus (HVTT) * Evidence of extrahepatic spread (EHS) * Being a candidate for curative treatments * Any condition representing a contraindication to TACE as determined by the investigators * Active or history of autoimmune disease or immune deficiency * Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding * A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment * Evidence of bleeding diathesis or significant coagulopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TACE Progression-Free Survival (TACE PFS) as Determined by Investigator | Randomization to untreatable progression or TACE failure/refractoriness or death (up to approximately 46 months) | TACE PFS is defined as the time from randomization to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first, as determined by the investigator (INV). |
| Overall Survival (OS) | Randomization to death from any cause (up to approximately 94 months) | Overall survival (OS) after enrollment is defined as the time from randomization to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Untreatable (unTACEable) Progression (TTUP) as Determined by Investigator | Randomization to untreatable (unTACEable) progression (up to approximately 46 months) | INV-assessed TTUP is defined as time from randomization to untreatable (unTACEable) progression, as determined by investigator. |
| Time to Progression (TTP) as Determined by Investigator | Randomization to unTACEable progression or TACE failure/refractoriness (up to approximately 46 months) | INV-assessed TTP is defined as the time from randomization to unTACEable progression or TACE failure/refractoriness (as defined above), as determined by investigator. |
| Time to Extrahepatic Spread (EHS) as Determined by Investigator | Randomization to first evidence of EHS (up to approximately 46 months) | INV-assessed time to EHS is defined as the time from randomization to the first evidence of EHS, as determined by investigator. |
| Objective Response Rate (ORR), as Determined by Investigator | Randomization up to approximately 46 months | Objective response (OR) is defined as a complete or partial response, as determined by investigator. |
| Duration of Responses (DOR) as Determined by Investigator | First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 46 months) | INV-assessed DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by INV. |
| Progression Free Survival (PFS) | Randomization to first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 94 monthsJ) | Progression free survival (PFS) is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. |
| Time to Deterioration (TTD) | Randomization to first deterioration (up to approximately 94 months) | TTD is defined as the time from randomization to first deterioration in the patient-reported GHS/QoL, physical function, or role function scales of the EORTC QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks. |
| Percentage of Participants With Adverse Events | Baseline up to approximately 94 months | — |
Countries
China, Japan
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed