A study to compare atezolizumab plus lenvatinib or sorafenib with lenvatinib or sorafenib alone in people with advanced and/or inoperable liver cancer (hepatocellular carcinoma) after previous treatment with atezolizumab plus bevacizumab

A Study of Atezolizumab With Lenvatinib or Sorafenib Versus Lenvatinib or Sorafenib Alone in Hepatocellular Carcinoma Previously Treated With Atezolizumab and Bevacizumab

  • Cancer
  • Hepatocellular Carcinoma (HCC)
  • Unresectable Hepatocellular Carcinoma
Please note that the recruitment status of the study at your site may differ from the overall study status because some study sites may recruit earlier than others.
Study Status:

Active, not recruiting

This study runs in
Cities
  • Aichi
  • Ankara
  • Athina
  • Bakirkoy Istanbul
  • Bangkok
  • Bern
  • Bologna
  • Brasschaat
  • Bruxelles
  • Bursa
  • Cairo Governorate
  • Calgary
  • Cebu City
  • Changsha City
  • Chiba
  • Córdoba
  • Edmonton
  • Firenze
  • Florianopolis
  • Frankfurt
  • Fukuoka
  • Fuzhou City
  • goyang-si
  • Grenoble Cedex 9
  • Guangzhou
  • Guangzhou City
  • Gyeonggi-do
  • Haifa
  • Hamilton
  • Hannover
  • Hefei Shi
  • Hiroshima
  • Hyogo
  • Innsbruck
  • Izmir
  • Kanagawa
  • Kuala Lumpur
  • Leuven
  • Lille
  • Liverpool
  • Ljubljana
  • London
  • Madrid
  • Mainz
  • Manchester
  • Marseille
  • Milano
  • Montpellier
  • Moscow
  • Nanjing City
  • Nantes
  • Napoli
  • Newcastle upon Tyne
  • Osaka
  • Oxford
  • Padova
  • Palermo
  • Palma De Mallorca
  • Pamplona iruña
  • Panagyurishte
  • Paris
  • pesochny
  • Pessac
  • Petach Tikva
  • Pisa
  • Plovdiv
  • Porto Alegre
  • Putrajaya
  • Rennes
  • Rio de Janeiro
  • Roeselare
  • Roma
  • Salzburg
  • San José
  • Santiago de Compostela
  • Seoul
  • Shanghai
  • Shenyang
  • sihhiye-ankara
  • São Paulo
  • Tainan City
  • Tallinn
  • Tampere
  • Tartu
  • Tel Aviv
  • Tianjin
  • Tochigi
  • Tokyo
  • Torino
  • Toronto
  • Toulouse Cedex 09
  • Tübingen
  • Ulm
  • València
  • Vandoeuvre Les Nancy
  • Wien
  • Zagreb
  • Zaragoza
  • Zhongzheng Dist.
  • Zürich
Trial Identifier:

NCT04770896 2023-503229-21-00 MO42541

  • A.O. S. Orsola Malpighi

    9 Via Giuseppe Massarenti40138BolognaItaly
  • A.O.U. Policlinico Paolo Giaccone

    129 Via del Vespro90127PalermoItaly
  • Ac?badem Altunizade Hastanesi

    1 Yurtcan Sokağı34662
  • Agioi Anargiroi Hospital of Kifissia

    14564
  • AirForce Specialized Hospital

    11391Cairo GovernorateEgypt
  • Anhui Province Cancer Hospital

    12345Hefei ShiChina
  • APHM

    13385MarseilleFrance
  • APHP - Hopital Saint Antoine

    75571ParisFrance
  • Arthur J.E. Child Comprehensive Cancer Center-Calgary

    3395 Hospital Dr NWT2N 4N2CalgaryCanada
  • AZ Delta (Campus Rumbeke)

    1 Deltalaan8800RoeselareBelgium
  • AZ KLINA

    100 Augustijnslei2930BrasschaatBelgium
  • Azienda Osp Uni Seconda Università Degli Studi Di Napoli

    80131NapoliItaly
  • Azienda Ospedaliera Ordine Mauriziano di Torino

    109 Corso Re Umberto10128TorinoItaly
  • Azienda Ospedaliera San Camillo Forlanini

    87 Circonvallazione Gianicolense00152RomaItaly
  • Azienda Ospedaliero-Universitaria Careggi

    1 Largo Piero Palagi50139FirenzeItaly
  • Azlenda Ospendaliero-Universitaria Pisana

    56100PisaItaly
  • Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji

    No:11 Dr. Tevfik Sağlam Cd34147Bakirkoy IstanbulTurkey
  • Beneficencia Portuguesa de Sao Paulo

    637 R. Maestro Cardim01321-00São PauloBrazil
  • Cebu Doctors' University Hospital

    6000Cebu CityPhilippines
  • Centre Eugene Marquis;Service d'oncologie

    35042RennesFrance
  • Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

    63 R. Menino Deus88020-210FlorianopolisBrazil
  • CH Saint Eloi

    80 Av. Augustin Fliche34295MontpellierFrance
  • CHA Bundang Medical Center

    13496Gyeonggi-doKorea, Republic of
  • Chi-Mei Medical Centre

    710Tainan CityTaiwan
  • Christie Hospital Nhs Trust

    M2O 4BXManchesterUnited Kingdom
  • CHRU de Lille - Hopital Claude Huriez

    59037LilleFrance
  • CHU Bordeaux

    33604PessacFrance
  • CHU de Nantes - Hotel Dieu

    1 Pl. Alexis-Ricordeau44093NantesFrance
  • CHU de Toulouse - Hôpital Rangueil

    2 Rue Charles Viguerie31059Toulouse Cedex 09France
  • CHU Grenoble Sud

    38043Grenoble Cedex 9France
  • Chulalongkorn Hospital

    1873 Thanon Rama IV10330BangkokThailand
  • Churchill Hospital

    OX3 7LEOxfordUnited Kingdom
  • Clinica CIMCA

    10103San JoséCosta Rica
  • Clinica Universidad de Navarra Madrid

    1 C. del Marquesado de Sta. Marta28027MadridSpain
  • Clinica Universitaria de Navarra

    36 Av. de Pío XII31008Pamplona iruñaSpain
  • Clinical Hospital Centre Zagreb

    12 Trg Kralja Tomislava10000ZagrebCroatia
  • Clinicas Oncologicas Integradas - COI

    108 R. Real Grandeza22290-160Rio de JaneiroBrazil
  • Cliniques Universitaires St-Luc

    10 Av. Hippocrate1200BruxellesBelgium
  • Complejo Hospitalario Universitario de Santiago (CHUS)

    s/n Rúa da Choupana15706Santiago de CompostelaSpain
  • Complex Oncological Center - Plovdiv, EOOD

    4004PlovdivBulgaria
  • Cross Cancer Institute

    11560 University AveT6G 1Z2EdmontonCanada
  • Ege Uni Medical Faculty Hospital

    No:9 Üniversite Cd.35100IzmirTurkey
  • Faculty of Med. Siriraj Hosp.

    10700BangkokThailand
  • Fondazione IRCCS Ospedale Maggiore Policlinico

    35 Via Francesco Sforza20122MilanoItaly
  • Fondazione Pascale

    52 Via Mariano Semmola80100
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    8 Largo Agostino Gemelli00168RomaItaly
  • Freeman Hospital

    NE7 7DNNewcastle upon TyneUnited Kingdom
  • FSBI "National Medical Research Center of Oncology N.N. Blokhin?

    115478MoscowRussian Federation
  • Fujian Provincial Hospital

    134 Dong Jie350001Fuzhou CityChina
  • Fujita Health University Hospital

    470-1192AichiJapan
  • Hacettepe Uni Medical Faculty Hospital

    06230sihhiye-ankaraTurkey
  • Hammersmith Hospital

    72 Du Cane RdW12 0HSLondonUnited Kingdom
  • Hiroshima University Hospital

    734-8551HiroshimaJapan
  • Hopital Paul Brousse

    94804
  • Hopitaux de Brabois - Gastro-Entereologie

    54511Vandoeuvre Les NancyFrance
  • Hospital Clinico San Carlos

    S/N Calle del Prof Martín Lagos28040MadridSpain
  • Hospital Erasme

    808 Rte de Lennik1070BruxellesBelgium
  • Hospital Felicio Rocho

    9530 Av. do Contorno30110-160
  • Hospital General Universitario Gregorio Marañon

    46 C. del Dr. Esquerdo28007MadridSpain
  • Hospital Moinhos de Vento

    910 R. Ramiro Barcelos90035-000Porto AlegreBrazil
  • Hospital Sao Lucas - PUCRS

    6690 Av. Ipiranga90610-000Porto AlegreBrazil
  • Hospital Son Llatzer

    km 4 C. de Manacor07198Palma De MallorcaSpain
  • Hospital Universitario la Fe

    106 Avinguda de Fernando Abril Martorell46026ValènciaSpain
  • Hospital Universitario Miguel Servet

    1-3 P.º de Isabel la Católica50009ZaragozaSpain
  • Hospital Universitario Reina Sofia

    s/n Av. Menéndez Pidal14004CórdobaSpain
  • Hunan Cancer Hospital

    410013Changsha CityChina
  • I.M.Sechenov First Moscow State Medical University (1st MSMU)

    119991
  • ICIMED Instituto de Investigación en Ciencias Médicas

    10108San JoséCosta Rica
  • Inselspital Bern Medizin Gastroenterologie

    20 Freiburgstrasse3010BernSwitzerland
  • Institute Kanser Negara (IKN)

    4 Jalan P762250PutrajayaMalaysia
  • IRCCS Istituto Oncologico Veneto (IOV)

    64 Via Gattamelata35128PadovaItaly
  • Japanese Red Cross Musashino Hospital

    180-8610TokyoJapan
  • Japanese Red Cross Society Himeji Hospital

    670-8540HyogoJapan
  • Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

    140 Han Zhong Lu210029Nanjing CityChina
  • Jichi Medical University Hospital

    329-0498TochigiJapan
  • Juravinski Cancer Centre

    699 Concession StL8V 5C2HamiltonCanada
  • Kindai University Hospital

    589-8511OsakaJapan
  • King College Hospital NHS Foundation Trust

    SE5 9RSLondonUnited Kingdom
  • Klinik Favoriten

    3 Kundratstraße1100WienAustria
  • Klinik Johann Wolfgang von Goethe Uni

    60590FrankfurtGermany
  • Kurume University Hospital

    830-0011FukuokaJapan
  • Laiko General Hospital Athen

    17 Agiou Thoma115 27AthinaGreece
  • LLC "Oncology scientific centre"

    197758pesochnyRussian Federation
  • Makati Medical Center

    2 Amorsolo Street1229
  • Med. Hochschule Hannover

    1 Carl-Neuberg-Straße30625HannoverGermany
  • Medipol Mega Üniversite Hastanesi Göztepe

    34214
  • Medizinische Universität Innsbruck

    3 Fritz-Pregl-Straße6020InnsbruckAustria
  • Memorial Ankara Hastanesi

    No: 4 1422. Sk.06520AnkaraTurkey
  • Moscow City Oncology Hospital #62

    125134
  • Multiprofile Hospital for Active Treatment Uni Hospital

    100 ul. "Georgi Benkovski"4500PanagyurishteBulgaria
  • Nanfang Hospital, Southern Medical University

    1838 Guang Zhou Da Dao Bei510515GuangzhouChina
  • National Cancer Center

    10408goyang-siKorea, Republic of
  • National Cancer Center Hospital East

    277-8577ChibaJapan
  • National Taiwan University Hospital

    7號 Zhongshan S Rd10048Zhongzheng Dist.Taiwan
  • North Estonia Medical Centre, Oncology and hematology Clinic

    13419TallinnEstonia
  • Osaka University Hospital

    565-0871OsakaJapan
  • Ospedale del Mare

    11 Via Enrico Russo80147NapoliItaly
  • Princess Margaret Cancer Center

    610 University AveM5G 2M9TorontoCanada
  • Rabin Medical Center

    39 Zeev Jabotinsky St4941492Petach TikvaIsrael
  • Rambam Health Care Campus

    8 HaAliya HaShniya St3109601HaifaIsrael
  • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

    33号 Bei Yuan Lu200127ShanghaiChina
  • Royal Free Hospital

    NW3 2QSLondonUnited Kingdom
  • Samsung Medical Center

    (0)6351SeoulKorea, Republic of
  • Severance Hospital, Yonsei University Health System

    03722SeoulKorea, Republic of
  • Shengjing Hospital of China Medical University

    36 San Hao Jie110004ShenyangChina
  • Sourasky Medical Center

    6 Weizmann St6423900Tel AvivIsrael
  • START Madrid. Centro Integral Oncologico Clara Campal

    10 C. de Oña28050MadridSpain
  • Tartu University Hospital

    8 Puusepa tn50406TartuEstonia
  • TAYS Radius rakennus

    6 Sädetie33520TampereFinland
  • The Clatterbridge Cancer Centre NHS Foundation Trust

    L7 8YALiverpoolUnited Kingdom
  • The First Affiliated Hospital, Sun Yat-sen University

    1 Zhong Shan Er Lu510080Guangzhou CityChina
  • The Medical City

    1600
  • Tianjin Cancer Hospital

    300060TianjinChina
  • Uludag Uni Hospital

    16059BursaTurkey
  • Uni Malaya Medical Center

    59100Kuala LumpurMalaysia
  • Uniklinik Mainz

    1 Langenbeckstraße55131MainzGermany
  • Uniklinikum Salzburg, LKH

    48 Müllner Hauptstraße5020SalzburgAustria
  • Universität Tübingen

    72076TübingenGermany
  • Universitätsklinikum St. Pölten

    40 Kremser Landstraße3100
  • Universitätsklinikum Ulm

    23 Albert-Einstein-Allee89081UlmGermany
  • Universitätsspital Zürich Medizin Gastroenterologie

    8091ZürichSwitzerland
  • University Medical Center Ljubljana

    7 Zaloška cesta1000LjubljanaSlovenia
  • UZ Leuven

    49 Herestraat3000LeuvenBelgium
  • Yokohama City University Medical Center

    232-0024KanagawaJapan
  • Zhongshan Hospital Fudan University

    180 Feng Lin Lu200032ShanghaiChina
    Show study locations

    The source of the below information is public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc.. It has been summarised and edited into simpler language. For more information about this clinical study see the For Expert tab on the specific ForPatients page or follow these links to https://clinicaltrials.gov and/or https://euclinicaltrials.eu and/or https://www.isrctn.com.

    The below information is taken directly from public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc., and has not been edited.

    Results Disclaimer

    Study 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.

    Hoffmann-La Roche Sponsor
    Phase 3 Phase
    NCT04770896, MO42541, 2023-503229-21-00 Study Identifier
    All Gender
    ≥18 Years Age
    No Healthy Volunteers

    1. Why is this study needed?

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Standard first medicine for inoperable HCC includes atezolizumab and bevacizumab which are widely used cancer immunotherapies (CITs). They help the body’s immune system to destroy cancer cells. Other treatments, such as sorafenib or lenvatinib are medicines that can block cancer growth. When first treatments do not work well, or stop working, treatment is switched to another therapy option. Currently, doctors do not know which medicines would work best as a next treatment for HCC after atezolizumab and bevacizumab stop working. This is why researchers are looking at new therapy options.

    This study aims to compare the effects of atezolizumab plus lenvatinib or sorafenib versus lenvatinib or sorafenib alone in people with HCC.

    2. Who can take part in this study?

    People (males and females) of at least 18 years old and diagnosed with advanced, metastatic or inoperable HCC, can take part in this study if they have previously received atezolizumab plus bevacizumab as treatment for HCC and have good liver function.

    People may not be able to take part in this study if they have had previous treatment with certain medications, have cancer that has spread to the brain or spinal cord and causes symptoms. People with certain medical conditions also may not be able to take part in the study, this includes a second type of cancer, autoimmune, heart, liver or lung diseases, or certain infections. Women who are pregnant or breastfeeding, cannot take part in this study.

    3. How does this study work?

    This clinical trial is recruiting people with HCC which has spread to surrounding tissues (called ‘advanced’), to other parts of the body (known as ‘metastatic’) or cannot be removed with surgery (called ‘inoperable’).

    Participants will be screened to check if they are able to participate in the study. The screening period will take place 28 days before the start of treatment.

    Everyone who joins this study will be split into two groups (Group A and Group B) randomly (like flipping a coin). Group A will be given atezolizimab, given as an infusion (into the vein) every 3 weeks, plus lenvatinib, given as pills which are taken every day OR sorafenib pills to be taken twice daily. Group B will be given lenvatinib, given as pills which are taken every day OR sorafenib pills to be taken twice daily. Participants will have an equal chance of being placed in either group. They will continue to receive treatment as long as there is clinical benefit. In both groups, whether participants get lenvatinib or sorafenib will depend on the study site, but all participants at each site will be given the same option.

    This is an open-label study. This means everyone involved, including the participant and the study doctor, will know the study treatment the participant has been given.

    During this study, the study doctor will see participants every 3 weeks while they are receiving treatment. They will see how well the treatment is working and any unwanted effects participants may have. Participants will have follow-up visits or telephone calls every 3 months, for 1 year after completing the study treatment, during which the study doctor will check on the participant’s well being. Total time of participation in the study will be approximately 1 and a half years. It depends on the clinical benefit from the allocated study treatment. Participants have the right to stop study treatment and leave the study at any time, if they wish to do so.

    4. What are the main results measured in this study?

    The main results measured in the study to assess if the medicine has worked how long participants live (overall survival) from the start of the study.

    Other key results measured in the study include:

    • The time between the start of the trial and cancer getting worse or loss of life for any reason (progression-free survival)
    • How many participants have a reduction of their cancer after treatment (objective response rate)
    • The duration between the start of a treatment and the point at which the cancer being treated progresses or worsens. (time to progression)
    • How much time there is between the participant’s cancer first responding to treatment and the cancer getting worse. (duration of response)
    • The time between the start of the trial and to a worsening health-related quality of life
    • The number, type, and seriousness of any side effects

    5. Are there any risks or benefits in taking part in this study?

    Taking part in the study may or may not make participants feel better. But the information collected in the study can help other people with similar health conditions in the future.

    It may not be fully known at the time of the study how safe and how well the study treatment works. The study involves some risks to the participant. But these risks are generally not greater than those related to routine medical care or the natural progression of the health condition. People interested in taking part will be informed about the risks and benefits, as well as any additional procedures or tests they may need to undergo. All details of the study will be described in an informed consent document. This includes information about possible effects and other options of treatment.

    Risks associated with the study drugs

    Participants may have unwanted effects from the drugs used in this study. These unwanted effects can be mild to severe, even life-threatening, and vary from person to person. During this study, participants will have regular check-ups to see if there are any unwanted effects.

    Participants will be told about the known unwanted effects of atezolizumab, lenvatinib and sorafenib, and possible unwanted effects based on human and laboratory studies or knowledge of similar medicines.

    Known unwanted effects of atezolizumab include inflammation as the medication is designed to increase the number of immune system cells in the body that can fight cancer. These cells may cause inflammation within the tumor, as well as in normal tissue, anywhere in the body. Other unwanted effects include back pain, cough, decreased appetite, diarrhea, fatigue, fever, headache, itching of the skin (pruritus), joint pain (arthralgia).

    Known unwanted effects of lenvatinib include high or low blood pressure, loss of appetite or weight loss, feeling sick (nausea) and being sick (vomiting), constipation, diarrhea, abdominal pain, indigestion, feeling very tired or weak, hoarse voice, swelling of the legs, rash.

    Known unwanted effects of sorafenib include diarrhea, feeling sick (nausea) and being sick (vomiting), feeling weak or tired (fatigue), pain (including mouth pain, abdominal pain, headache, bone pain, tumor pain), hair loss (alopecia).

    The study medicine(s) may be harmful to an unborn baby. Women and men must take precautions to avoid exposing an unborn baby to the study treatment.

    Study 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.

    Hoffmann-La Roche Sponsor
    Phase 3 Phase
    NCT04770896, MO42541, 2023-503229-21-00 Trial Identifier
    Atezolizumab, Lenvatinib, Sorafenib Treatments
    Unresectable Hepatocellular Carcinoma Condition
    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

    Eligibility Criteria

    All Gender
    ≥18 Years Age
    No Healthy Volunteers
    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

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