Clinical trial NCT04770896: A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
Official title: A Phase III, Open-Label, Randomized Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Unresectable Hepatocellular Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-02-25
Enrollment: 554
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization until death from any cause (approximately 42 months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Randomization until the first occurrence of disease progression or death from any cause whichever occurs first (approximately 42 months)
measure: Confirmed Objective Response Rate (ORR)
timeFrame: Approximately 42 months
measure: Time to Progression (TTP)
timeFrame: Randomization until the first occurrence of disease progression (approximately 42 months)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Time to confirmed deterioration (TTCD)
timeFrame: 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)
measure: Percentage of Participants With Adverse Events
timeFrame: Throughout study duration (approximately 42 months)
measure: Percentage of Participants With Adverse Events for Combination Treatment, Adverse Events Related to Atezolizumab, and TKI-Related Adverse Events
timeFrame: Throughtout study (approximately 42 months)
measure: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
timeFrame: Throughout study (approximately 42 months)
measure: Serum Concentration of Atezolizumab
timeFrame: At pre-defined intervals from first administration of study drug to approximately 42 months
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Salzburg
country: Austria
facility: Uniklinikum Salzburg, LKH
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Wien
country: Austria
facility: Klinik Favoriten
city: Brasschaat
country: Belgium
facility: AZ KLINA
city: Bruxelles
country: Belgium
facility: Hospital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Belo Horizonte
country: Brazil
facility: Hospital Felicio Rocho
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: Rio Grande Do Sul
city: Florianopolis
country: Brazil
facility: Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
state: Santa Catarina
city: São Paulo
country: Brazil
facility: Beneficencia Portuguesa de Sao Paulo
city: Panagyurishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Uni Hospital
city: Plovdiv
country: Bulgaria
facility: Complex Oncological Center - Plovdiv, EOOD
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Center-Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Changsha City
country: China
facility: Hunan Cancer Hospital
city: Fuzhou City
country: China
facility: Fujian Provincial Hospital
city: Guangzhou City
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Hefei
country: China
facility: Anhui Province Cancer Hospital
city: Nanjing City
country: China
facility: Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shanghai
country: China
facility: Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: ShenYang
country: China
facility: Shengjing Hospital of China Medical University
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: San Jose
country: Costa Rica
facility: Clinica CIMCA
city: San Jose
country: Costa Rica
facility: ICIMED Instituto de Investigación en Ciencias Médicas
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb
city: Cairo
country: Egypt
facility: AirForce Specialized Hospital
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre, Oncology and hematology Clinic
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Tampere
country: Finland
facility: TAYS Radius rakennus
city: GRENOBLE Cedex 9
country: France
facility: CHU Grenoble Sud
city: Lille
country: France
facility: CHRU de Lille - Hopital Claude Huriez
city: Marseille
country: France
facility: APHM
city: Montpellier
country: France
facility: CH Saint Eloi
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Paris
country: France
facility: APHP - Hopital Saint Antoine
city: Pessac
country: France
facility: CHU Bordeaux
city: Rennes
country: France
facility: Centre Eugene Marquis;Service d'oncologie
city: Toulouse Cedex 09
country: France
facility: CHU de Toulouse - Hôpital Rangueil
city: Vandoeuvre-les-nancy
country: France
facility: Hopitaux de Brabois - Gastro-Entereologie
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Frankfurt
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni
city: Hannover
country: Germany
facility: Med. Hochschule Hannover
city: Mainz
country: Germany
facility: Uniklinik Mainz
city: Tübingen
country: Germany
facility: Universität Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Athens
country: Greece
facility: Laiko General Hospital Athen
city: Nea Kifissia
country: Greece
facility: Agioi Anargiroi Hospital of Kifissia
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center
city: Napoli
country: Italy
facility: Fondazione Pascale
state: Campania
city: Napoli
country: Italy
facility: Azienda Osp Uni Seconda Università Degli Studi Di Napoli
state: Campania
city: Napoli
country: Italy
facility: Ospedale del Mare
state: Campania
city: Bologna
country: Italy
facility: A.O. S. Orsola Malpighi
state: Emilia-Romagna
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino
state: Piemonte
city: Palermo
country: Italy
facility: A.O.U. Policlinico Paolo Giaccone
state: Sicilia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
state: Toscana
city: Pisa
country: Italy
facility: Azlenda Ospendaliero-Universitaria Pisana
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Aichi
country: Japan
facility: Fujita Health University Hospital
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka
country: Japan
facility: Kurume University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hyogo
country: Japan
facility: Japanese Red Cross Society Himeji Hospital
city: Kanagawa
country: Japan
facility: Yokohama City University Medical Center
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital
city: Tokyo
country: Japan
facility: Japanese Red Cross Musashino Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Kuala Lumpur
country: Malaysia
facility: Uni Malaya Medical Center
state: FED. Territory OF Kuala Lumpur
city: Putrajaya
country: Malaysia
facility: Institute Kanser Negara (IKN)
state: FED. Territory OF Kuala Lumpur
city: Cebu City
country: Philippines
facility: Cebu Doctors' University Hospital
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Pasig City
country: Philippines
facility: The Medical City
city: Moscow
country: Russian Federation
facility: FSBI "National Medical Research Center of Oncology N.N. Blokhin?
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: I.M.Sechenov First Moscow State Medical University (1st MSMU)
state: Moskovskaja Oblast
city: Ljubljana
country: Slovenia
facility: University Medical Center Ljubljana
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Islas Baleares
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
state: LA Coruna
city: Pamplona/iruña
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra Madrid
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal
city: Valencia
country: Spain
facility: Hospital Universitario la Fe
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Bern
country: Switzerland
facility: Inselspital Bern Medizin Gastroenterologie
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich Medizin Gastroenterologie
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Centre
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital
city: Bangkok
country: Thailand
facility: Faculty of Med. Siriraj Hosp.
city: Ankara
country: Turkey
facility: Memorial Ankara Hastanesi
city: Ba?c?lar
country: Turkey
facility: Medipol Mega Üniversite Hastanesi Göztepe
city: Bakirkoy / Istanbul
country: Turkey
facility: Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
city: Bursa
country: Turkey
facility: Uludag Uni Hospital
city: Istanbul
country: Turkey
facility: Ac?badem Altunizade Hastanesi
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: King College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: