Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Collaborator:
-
Studienleiter
Salah Eddin Al-Batran, Prof. Dr. Study Director Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Germany Peter Galle, Prof. Dr. Principal Investigator Universitätsmedizin Mainz, Germany Jordi Bruix, Prof. Dr. Principal Investigator Barcelona Clinic Liver Cancer, Universitat de Barcelona, Spain
Kontakt
Peter Galle, Prof. Dr. Kontakt: Phone: 0049 6131 177275 E-Mail: peter.galle@unimedizin-mainz.de» Kontaktdaten anzeigen Johanna Riedel, Dr. Kontakt: Phone: 0049 697 601 4635 E-Mail: riedel.johanna@ikf-khnw.de» Kontaktdaten anzeigen
Studienlocations (3 von 68)
University Hospital RWTH Aachen 52074 Aachen GermanyRekrutierend» Google-MapsKlinikum St. Marien Amberg 92224 Amberg (Bayern) GermanyRekrutierend» Google-MapsVivantes Klinikum Neukölln 12351 Berlin (Berlin) GermanyRekrutierend» Google-Maps
Universitätsklinikum Bochum 44892 Bochum (Nordrhein-Westfalen) GermanyRekrutierend» Google-MapsUniversitätsklinikum Dresden 01307 Dresden (Sachsen) GermanyRekrutierend» Google-MapsDarmkrebszentrum Universitätsklinikum Düsseldorf Moorenstraße 5 40225 Düsseldorf DeutschlandRekrutierend» Google-MapsHautkrebszentrum Universitätsklinikum Erlangen Ulmenweg 18 91054 Erlangen (Bayern) DeutschlandRekrutierend» Google-MapsInterdisziplinäres Brustzentrum am Klinikum Esslingen Hirschlandstraße 97 73730 Esslingen am Neckar (Baden-Württemberg) DeutschlandRekrutierend» Google-MapsOnkologisches Zentrum Krankenhaus Nordwest Steinbacher Hohl 2-26 60488 Frankfurt am Main DeutschlandRekrutierend» Google-MapsUniversitätsklinikum Frankfurt 60590 Frankfurt (Hessen) GermanyRekrutierend» Google-MapsUniversitätsklinikum Freiburg 79106 Freiburg (Baden-Württemberg) GermanyRekrutierend» Google-MapsBrustzentrum der Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen DeutschlandRekrutierend» Google-MapsLeberkrebszentrum Medizinische Hochschule Hannover Carl-Neuberg-Straße 1 30625 Hannover DeutschlandRekrutierend» Google-MapsKlinikum Konstanz 78464 Konstanz (Baden-Württemberg) GermanyRekrutierend» Google-MapsKrankenhaus Maria-Hilf Krefeld 47805 Krefeld (Nordrhein-Westfalen) GermanyRekrutierend» Google-MapsLungenkrebszentrum Uniklinik Köln / Solingen Kerpener Straße 62 50937 Köln DeutschlandRekrutierend» Google-MapsDarmkrebszentrum am Universitätsklinikum Schleswig-Holstein, Campus Lübeck Ratzeburger Allee 160 23562 Lübeck DeutschlandRekrutierend» Google-MapsDarmkrebszentrum der Universitätsmedizin Mainz Langenbeckstraße 1 55131 Mainz DeutschlandRekrutierend» Google-Maps Ansprechpartner: Peter Galle, Prof. Dr. Phone: 00496131177275 E-Mail: peter.galle@unimedizin-mainz.de» Ansprechpartner anzeigenDarmkrebszentrum Universitätsklinikum Mannheim Theodor-Kutzer-Ufer 1 - 3 68167 Mannheim DeutschlandRekrutierend» Google-MapsUniversitätsklinikum Marburg 35043 Marburg (Hessen) GermanyRekrutierend» Google-MapsKlinikum rechts der Isar München 81675 München (Bayern) GermanyRekrutierend» Google-MapsKlinikum Mutterhaus Trier 54290 Trier (Rheinland-Pfalz) GermanyRekrutierend» Google-MapsDarmzentrum am Krankenhaus der Barmherzigen Brüder Trier Nordallee 1 54292 Trier DeutschlandRekrutierend» Google-MapsSt. Josefs Hospital Wiesbaden 65189 Wiesbaden (Hessen) GermanyRekrutierend» Google-MapsOnkologisches Zentrum Universitätsklinikum Würzburg Josef-Schneider-Straße 6 97080 Würzburg DeutschlandRekrutierend» Google-MapsLKH - Univ. Klinikum Graz 8036 Graz AustriaRekrutierend» Google-MapsMedzinische Universität Innsbruck 6020 Innsbruck AustriaRekrutierend» Google-MapsKlinikum Klagenfurt am Wörthersee 9020 Klagenfurt AustriaRekrutierend» Google-MapsOrdensklinikum Linz 4010 Linz AustriaRekrutierend» Google-MapsUniversitätsklinikum St. Pölten 3100 St. Pölten AustriaRekrutierend» Google-MapsMedizinische Universität Wien 1090 Wien AustriaRekrutierend» Google-MapsInstitut Sainte-Catherine 84918 Avignon FranceRekrutierend» Google-MapsHôpital Jean-Verdier Avicenne 93000 Bobigny FranceRekrutierend» Google-MapsCHU Bordeaux 33000 Bordeaux FranceRekrutierend» Google-MapsCHU Clermont-Ferrand CHU Estaing 63100 Clermont-Ferrand FranceRekrutierend» Google-MapsBeaujon Hospital 92110 Clichy FranceRekrutierend» Google-MapsCHU Grenoble 38700 Grenoble FranceRekrutierend» Google-MapsCroix-Rousse Hopital 69004 Lyon FranceRekrutierend» Google-MapsSaint Joseph Hopital - Marseille 13008 Marseille FranceRekrutierend» Google-MapsHôpital Universitaire Pitié Salpêtrière 75013 Paris FranceRekrutierend» Google-MapsCentre Hépato-biliaire Paul Brousse 94800 Villejuif FranceRekrutierend» Google-MapsPoliclinico S. Orsola Bologna 40138 Bologna ItalyRekrutierend» Google-MapsInstituto Tumori della Romagna IRST IRCCS 47014 Meldola ItalyRekrutierend» Google-MapsPoliclinico di Milano 20122 Milano ItalyRekrutierend» Google-MapsAOUI Verona 37126 Verona ItalyRekrutierend» Google-MapsHokkaido University Hospital 060-8648 Hokkaido JapanRekrutierend» Google-MapsKobe University Hospital 650-0017 Kobe JapanRekrutierend» Google-MapsKumamoto University Hospital 860-8556 Kumamoto JapanRekrutierend» Google-MapsUniversity Hospital Kyoto Prefectural University of Medicine 602-8566 Kyoto JapanRekrutierend» Google-MapsNagasaki University Hospital 852-8501 Nagasaki JapanRekrutierend» Google-MapsKindai University Hospital 589-8511 Osaka JapanRekrutierend» Google-MapsSaitama Medical University Hospital 350-0451 Saitama JapanRekrutierend» Google-MapsFujita Health University Hospital 470-1192 Toyoake JapanRekrutierend» Google-MapsYamaguchi University Hospital 755-0046 Ube JapanRekrutierend» Google-MapsHospital Universitario de Alicante 03010 Alicante SpainRekrutierend» Google-MapsHospital Infanta Cristina 06080 Badajoz SpainRekrutierend» Google-MapsHospital Universitari Vall d'Hebrón 08035 Barcelona SpainRekrutierend» Google-MapsBarcelona Clinic Liver Cancer, Universitat de Bracelona 08036 Barcelona SpainRekrutierend» Google-Maps Ansprechpartner: Jordi Bruix, Prof. Dr. E-Mail: jbruix@clinic.cat» Ansprechpartner anzeigenHospital Puerta del Mar 11009 Cadiz SpainRekrutierend» Google-MapsHospital de Jaen 23007 Jaén SpainRekrutierend» Google-MapsHospital Universitario Gregorio Marañon 28007 Madrid SpainRekrutierend» Google-MapsHospital Universitario Ramón y Cajal 28034 Madrid SpainRekrutierend» Google-MapsHospital Fundación Jimenez Diaz 28040 Madrid SpainRekrutierend» Google-MapsHospital Universitario Puerta de Hierro Majadahonda 28222 Madrid SpainRekrutierend» Google-MapsHospital de Alcorcón 28922 Madrid SpainRekrutierend» Google-MapsHospital de Málaga 29010 Malaga SpainRekrutierend» Google-MapsHospital Marqués de Valdecilla 39008 Santander SpainRekrutierend» Google-MapsHospital Universitario Virgen del Rocío 41013 Sevilla SpainRekrutierend» Google-Maps
1. Time to failure of treatment strategy (Time Frame - 48 months - assessed every 8 weeks (±7days)): The primary endpoint is defined as the time from randomization until death or need for a further therapeutic option, defined for each arm as follows:
Arm A: Time from randomization until the failure of strategy does not allow for further treatment with atezolizumab + bevacizumab; or death, whichever comes first.
Arm B: Time from randomization until the failure of strategy does not allow for further TACE therapy; or death, whichever comes first.
Failure of strategy (in brief): failure of strategy is reached in case of progressive disease accompanied by any of the following: loss of clinical benefit, unacceptable toxicity, liver function deterioration, therapy not further applicable for other reasons.
Secondary outcome:
1. Overall survival (OS) (Time Frame - 48 months): Time from the date of randomization until the date of death due to any cause. A subject who has not died will be censored at last known date alive.
2. Overall Survival Rate at 24 months (OS@24) (Time Frame - 24 months): The proportion of patients assigned to a treatment arm known to be alive at 24 months after randomization.
3. Objective Response Rate (ORR) (Time Frame - 48 months): The proportion of patients assigned to a treatment arm with a confirmed best response of Complete Response (CR) or Partial Response (PR). Response will be assessed according to HCC mRECIST.
4. Time to Progression (TTP) (Time Frame - 48 months): Time from the date of randomization until the date of first objective disease progression. Subjects who have not progressed will be censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. Subjects who die without experiencing a progress first will be censored on their date of death.
5. Time to loss of systemic treatment options (TTSYS) (Time Frame - 24 months): Time from the date of randomization until the date the patient reaches a state of being unfit for any subsequent systemic treatment option (BSC as only option left) or the date of death whichever occurs first. Subjects who end systemic treatment at their own request will be censored at the day of end of systemic treatment. Subjects who are lost to follow-up will be censored at the date last known to be systemically treated.
6. Progression free survival (PFS) (Time Frame - 48 months): Time from the date of randomization until the date of first objective disease progression or death. Subjects who did not progress or die will be censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy.
7. Duration of Treatment (Time Frame - 24 months): From start of treatment to permanent discontinuation of the treatment arms A and B.
8. Duration of Response (DOR) (Time Frame - 48 months): Time from initial response to progressive disease or death in patients in treatment arms A and B with a confirmed best response of Complete Response (CR) or Partial Response (PR) according to HCC mRECIST. Subjects who did not progress or die will be censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy.
9. Time to deterioration of liver function (Time Frame - 48 months): Time from the date of randomization until liver function deterioration is registered according to definition given for failure of strategy. Only patients experiencing a deterioration of liver function are included into this analysis
10. Treatment-related and -unrelated toxicities (AEs, SAEs) according to NCI CTCAE v5.0 (Time Frame - 48 months): Summary of adverse events by treatment arm and CTCAE (version 5.0) grade and frequency of clinically significant abnormal laboratory parameters.
11. QoL (EORTC QLQ-C30 and HCC18 sub-questionnaire) (Time Frame - 48 months): QoL mean values and response as well as time to symptom deterioration (TTSD) defined as the time interval between randomization and the first decrease by ≥ 10-points. All randomly assigned patients with a baseline and at least one post-baseline assessment will be included in TTSD analyses. Patients without observed deterioration will be censored at the time of their last QoL assessment.
Experimental: Systemic therapy with atezolizumab + bevacizumab Patients receive atezolizumab 1200 mg flat dose plus bevacizumab 15 mg/kg given intravenously every 3 weeks until failure of strategy, participant request, or withdrawal of consent for a maximum of up to 24 months.
The discontinuation of one of the study drugs for toxicity reasons does not qualify as failure of treatment strategy as long as the other drug can be continued according to protocol.
Active Comparator: Locoregional therapy with TACE Patients will receive initial TACE and - if required to achieve or improve an objective response - a second TACE after 8 weeks (±7 days window). Thereafter, additional TACE can be applied on demand until failure of strategy, participant request, or withdrawal of consent for a maximum of up to 24 months.
TACE must be discontinued in cases of technical difficulties making additional TACE impossible.
Only conventional TACE (cTACE) and drug-eluting bead TACE (DEB-TACE) approaches are accepted as TACE therapy. However, consistency in the TACE procedure and the use of the chemotherapeutic agent has to be maintained for each individual patient.