Unresectable Hepatocellular Carcinoma
Conditions
Brief summary
This is a Phase III, open-label, multicenter, randomized, two-arm study designed to evaluate the efficacy and safety of atezolizumab plus either lenvatinib or sorafenib versus lenvatinib or sorafenib alone in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have progressed on prior systemic treatment with atezolizumab plus bevacizumab combination.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
DRUGLenvatinib
Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of \< 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of ≥ 60 kg will receive a daily dose of 12 mg.
DRUGSorafenib
Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle.
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
* Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients. * Disease progression following prior atezolizumab plus bevacizumab combination treatment for HCC, for at least 4 consecutive treatment cycles, and 2 subsequent tumor assessments. It is required that at least 1 tumor assessment shows either stable disease (SD), partial response (PR), or complete response (CR). * At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 7 days prior to randomization * Child-Pugh class A within 7 days prior to randomization * Adequate hematologic and end-organ function
Exclusion criteria
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. * History of leptomeningeal disease * History of hepatic encephalopathy, preceding 6 months, unresponsive to therapy within 3 days * Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC * History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization until death from any cause (approximately 42 months) | Overall survival (OS) is defined as the time from randomization into the study to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months) | Progression free survival (PFS) is defined as the time from randomization into the study to the first occurrence of disease progression or death from any cause (whichever occurs first). |
| Confirmed Objective Response Rate (ORR) | Approximately 42 months | Confirmed Objective Response Rate (ORR) is defined as the proportion of patients with a best response of either complete or partial response. |
| Time to Progression (TTP) | Randomization until the first occurrence of disease progression (approximately 42 months) | Time to Progression (TTP) is defined as the time from randomization to the first occurrence of disease progression. |
| Duration of Response (DOR) | Time from the first occurrence of a confirmed documented objective response to disease progression or death from any cause whichever occurs first (approximately 42 months) | Duration of Response (DOR) is defined as the time from the first occurrence of a documented confirmed objective response to disease progression or death from any cause (whichever occurs first). |
| Time to confirmed deterioration (TTCD) | Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death from any cause wthin 3 weeks or 6 weeks (approximately 42 months) | Time to confirmed deterioration (TTCD), of health-related quality of life (HRQoL), is defined as the time from randomization to first confirmed deterioration (decrease from baseline of ≥ 10 points) maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks (if Cycle 1-6) or 6 weeks (if after Cycle 6) in the following European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) scales (separately): physical function, role function, and GHS/QoL. |
| Percentage of Participants With Adverse Events | Throughout study duration (approximately 42 months) | — |
| Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events | Throughtout study (approximately 42 months) | — |
| Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab | Throughout study (approximately 42 months) | — |
| Serum Concentration of Atezolizumab | At pre-defined intervals from first administration of study drug to approximately 42 months | — |
Countries
Austria, Belgium, Brazil, Bulgaria, Canada, China, Costa Rica, Croatia, Egypt, Estonia, Finland, France, Germany, Greece, Israel, Italy, Japan, Malaysia, Philippines, Russia, Slovenia, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed