A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
- Conditions
- Unresectable Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT04770896
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 554
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Lenvatinib or Sorafenib Atezolizumab Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Atezolizumab + Lenvatinib or Sorafenib Lenvatinib Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Atezolizumab + Lenvatinib or Sorafenib Sorafenib Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Lenvatinib or Sorafenib Lenvatinib Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Lenvatinib or Sorafenib Sorafenib Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Percentage of Participants With Adverse Events Throughout study duration (approximately 42 months) Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab Throughout study (approximately 42 months) 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.
Serum Concentration of Atezolizumab At pre-defined intervals from first administration of study drug to 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)
Trial Locations
- Locations (122)
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria
Uniklinikum Salzburg, LKH
🇦🇹Salzburg, Austria
Universitätsklinikum St. Pölten
🇦🇹St. Pölten, Austria
Klinik Favoriten
🇦🇹Wien, Austria
AZ KLINA
🇧🇪Brasschaat, Belgium
Hospital Erasme
🇧🇪Bruxelles, Belgium
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
Hospital Felicio Rocho
🇧🇷Belo Horizonte, Minas Gerais, Brazil
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