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)
Fujian Provincial Hospital
🇨🇳Fuzhou City, China
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
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
🇧🇷Florianopolis, Santa Catarina, Brazil
Beneficencia Portuguesa de Sao Paulo
🇧🇷São Paulo, Brazil
Multiprofile Hospital for Active Treatment Uni Hospital
🇧🇬Panagyurishte, Bulgaria
Complex Oncological Center - Plovdiv, EOOD
🇧🇬Plovdiv, Bulgaria
Arthur J.E. Child Comprehensive Cancer Center-Calgary
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Hunan Cancer Hospital
🇨🇳Changsha City, China
The First Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou City, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, China
Anhui Province Cancer Hospital
🇨🇳Hefei, China
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
🇨🇳Nanjing City, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
Shengjing Hospital of China Medical University
🇨🇳ShenYang, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
Clinica CIMCA
🇨🇷San Jose, Costa Rica
ICIMED Instituto de Investigación en Ciencias Médicas
🇨🇷San Jose, Costa Rica
Clinical Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
AirForce Specialized Hospital
🇪🇬Cairo, Egypt
North Estonia Medical Centre, Oncology and hematology Clinic
🇪🇪Tallinn, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
TAYS Radius rakennus
🇫🇮Tampere, Finland
CHU Grenoble Sud
🇫🇷GRENOBLE Cedex 9, France
CHRU de Lille - Hopital Claude Huriez
🇫🇷Lille, France
APHM
🇫🇷Marseille, France
CH Saint Eloi
🇫🇷Montpellier, France
CHU de Nantes - Hotel Dieu
🇫🇷Nantes, France
APHP - Hopital Saint Antoine
🇫🇷Paris, France
CHU Bordeaux
🇫🇷Pessac, France
Centre Eugene Marquis;Service d'oncologie
🇫🇷Rennes, France
CHU de Toulouse - Hôpital Rangueil
🇫🇷Toulouse Cedex 09, France
Hopitaux de Brabois - Gastro-Entereologie
🇫🇷Vandoeuvre-les-nancy, France
Hopital Paul Brousse
🇫🇷Villejuif, France
Klinik Johann Wolfgang von Goethe Uni
🇩🇪Frankfurt, Germany
Med. Hochschule Hannover
🇩🇪Hannover, Germany
Uniklinik Mainz
🇩🇪Mainz, Germany
Universität Tübingen
🇩🇪Tübingen, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Laiko General Hospital Athen
🇬🇷Athens, Greece
Agioi Anargiroi Hospital of Kifissia
🇬🇷Nea Kifissia, Greece
Rambam Health Care Campus
🇮🇱Haifa, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Fondazione Pascale
🇮🇹Napoli, Campania, Italy
Azienda Osp Uni Seconda Università Degli Studi Di Napoli
🇮🇹Napoli, Campania, Italy
Ospedale del Mare
🇮🇹Napoli, Campania, Italy
A.O. S. Orsola Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Lazio, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Lazio, Italy
Fondazione IRCCS Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera Ordine Mauriziano di Torino
🇮🇹Torino, Piemonte, Italy
A.O.U. Policlinico Paolo Giaccone
🇮🇹Palermo, Sicilia, Italy
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Firenze, Toscana, Italy
Azlenda Ospendaliero-Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
IRCCS Istituto Oncologico Veneto (IOV)
🇮🇹Padova, Veneto, Italy
Fujita Health University Hospital
🇯🇵Aichi, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Kurume University Hospital
🇯🇵Fukuoka, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Japanese Red Cross Society Himeji Hospital
🇯🇵Hyogo, Japan
Yokohama City University Medical Center
🇯🇵Kanagawa, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Jichi Medical University Hospital
🇯🇵Tochigi, Japan
Japanese Red Cross Musashino Hospital
🇯🇵Tokyo, Japan
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
CHA Bundang Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Uni Malaya Medical Center
🇲🇾Kuala Lumpur, FED. Territory OF Kuala Lumpur, Malaysia
Institute Kanser Negara (IKN)
🇲🇾Putrajaya, FED. Territory OF Kuala Lumpur, Malaysia
Cebu Doctors' University Hospital
🇵🇭Cebu City, Philippines
Makati Medical Center
🇵🇭Makati City, Philippines
The Medical City
🇵🇭Pasig City, Philippines
FSBI "National Medical Research Center of Oncology N.N. Blokhin?
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Moscow City Oncology Hospital #62
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
I.M.Sechenov First Moscow State Medical University (1st MSMU)
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
University Medical Center Ljubljana
🇸🇮Ljubljana, Slovenia
Hospital Son Llatzer
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
🇪🇸Santiago de Compostela, LA Coruna, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona/iruña, Navarra, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Clinica Universidad de Navarra Madrid
🇪🇸Madrid, Spain
START Madrid. Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario la Fe
🇪🇸Valencia, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Inselspital Bern Medizin Gastroenterologie
🇨🇭Bern, Switzerland
Universitätsspital Zürich Medizin Gastroenterologie
🇨🇭Zürich, Switzerland
Chi-Mei Medical Centre
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Zhongzheng Dist., Taiwan
Chulalongkorn Hospital
🇹🇭Bangkok, Thailand
Faculty of Med. Siriraj Hosp.
🇹🇭Bangkok, Thailand
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Medipol Mega Üniversite Hastanesi Göztepe
🇹🇷Ba?c?lar, Turkey
Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
🇹🇷Bakirkoy / Istanbul, Turkey
Uludag Uni Hospital
🇹🇷Bursa, Turkey
Ac?badem Altunizade Hastanesi
🇹🇷Istanbul, Turkey
Ege Uni Medical Faculty Hospital
🇹🇷Izmir, Turkey
Hacettepe Uni Medical Faculty Hospital
🇹🇷Sihhiye/Ankara, Turkey
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
King College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Christie Hospital Nhs Trust
🇬🇧Manchester, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom