Clincosm LogoSign in Get a demo

IMbrave050: A Study of Atezolizumab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04102098
Collaborator
(none)
668
Enrollment
139
Locations
2
Arms
90.5
Anticipated Duration (Months)
4.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
668 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multicenter, Randomized, Open-Label Study of Atezolizumab (Anti-PD-L1 Antibody) Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation
Actual Study Start Date :
Dec 31, 2019
Anticipated Primary Completion Date :
Sep 28, 2023
Anticipated Study Completion Date :
Jul 16, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (atezolizumab plus bevacizumab)

Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.

Drug: Atezolizumab
Atezolizumab 1200 mg will be administered by IV infusion on Day 1 of each 21-day cycle.
Other Names:
  • Tecentriq

    • Drug: Bevacizumab
    Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
    Other Names:
  • Avastin

    		•
    No Intervention: Arm B (active surveillance)

    Active surveillance of participants.

    Outcome Measures

    Primary Outcome Measures

    1. Recurrence-Free Survival (RFS), as Determined by IRF [Baseline up to approximately 39 months]

      RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an IRF, or death from any cause (whichever occurs first).

    Secondary Outcome Measures

    1. Overall Survival (OS) [Baseline up to approximately 91 months]

      OS is defined as the time from randomization to death from any cause.

    2. RFS as Determined by the Investigator [Baseline up to approximately 91 months]

      RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an investigator, or death from any cause (whichever occurs first).

    3. Time to Recurrence (TTR) [Baseline up to approximately 91 months]

      TTR defined as the time from randomization to first documented occurrence of intrahepatic or extrahepatic HCC, as determined by the investigator and by an IRF.

    4. RFS Rate at 24 and 36 Months, as Assessed by the IRF [Randomization up to 24 months and up to 36 months]

    5. RFS Rate at 24 and 36 Months, as Assessed by the Investigator [Randomization up to 24 months and up to 36 months]

    6. OS Rate at 24 and 36 Months [Baseline to 24 and 36 months]

      OS rate defined as the proportion of patients who have not experienced death from any cause at 24 and 36 months after randomization.

    7. Time to Extrahepatic Spread (EHS) or Macrovascular Invasion [Baseline up to approximately 91 months]

      Time to EHS or macrovascular invasion after randomization, defined as the time from randomization to the first appearance of EHS or macrovascular invasion, as determined by the investigator.

    8. RFS in Pd-L1-High Subgroup [Baseline up to approximately 91 months]

      RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup.

    9. Percentage of Participants With Adverse Events [Baseline up to approximately 91 months]

    10. Serum Concentration of Atezolizumab [Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16 (each cycle is 21 days)]

    11. Number of Participants with Anti-Drug Antibodies (ADAs) to Atezolizumab [Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16 (each cycle is 21 days)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participants with a first diagnosis of HCC who have undergone either a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only) within 4-12 weeks prior to randomization

    • Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA only)

    • Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread

    • Absence of extrahepatic spread as confirmed by CT or MRI scan of the chest, abdomen, pelvis, and head prior to and following curative procedure

    • Full recovery from surgical resection or ablation within 4 weeks prior to randomization

    • High risk for HCC recurrence after resection or ablation

    • For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization

    • For patients with resected HCC, availability of a representative baseline tumor tissue sample

    • ECOG Performance Status of 0 or 1

    • Child-Pugh Class A status

    • Adequate hematologic and end-organ function

    • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods

    • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

    Exclusion Criteria:

    • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

    • Evidence of residual, recurrent, or metastatic disease at randomization

    • Clinically significant ascites

    • History of hepatic encephalopathy

    • Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization

    • Have received more than 1 cycle of adjuvant TACE following surgical resection

    • Active or history of autoimmune disease or immune deficiency

    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

    • Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina

    • 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

    • Active tuberculosis

    • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications

    • Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle 1.

    • Co-infection with HBV and HCV

    • Co-infection with HBV and hepatitis D viral infection

    • Clinical significant uncontrolled or symptomatic hypercalcemia

    • Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE

    • Treatment with systemic immunostimulatory or immunosuppressive agents

    • Inadequately controlled arterial hypertension

    • History of hypertensive crisis or hypertensive encephalopathy

    • Significant vascular disease

    • Evidence of bleeding diathesis or significant coagulopathy

    • Current or recent use of aspirin or full-dose oral or parenteral anticoagulants

    • Core biopsy within 3 days of Day 1 of Cycle 1

    • History of GI fistula, GI perforation, or intra-abdominal abscess

    • Serious non-healing or dehiscing wound

    • Major surgical procedure within four weeks

    • Chronic daily treatment with a non-steroidal anti-inflammatory drug

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kaiser Permanente Los Angeles Los Angeles California United States 90027
    2 Mercy Medical Center Baltimore Maryland United States 21202
    3 Henry Ford Health System Detroit Michigan United States 48202
    4 Columbia University Medical Center New York New York United States 10032
    5 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    6 The University of Texas Southwestern Medical Center at Dallas Dallas Texas United States 75390
    7 MD Anderson Cancer Center Houston Texas United States 77030
    8 Swedish Cancer Inst. Seattle Washington United States 98104
    9 St Vincent's Hospital Sydney Darlinghurst New South Wales Australia 2010
    10 Riverina Cancer Care Centre Wagga Wagga New South Wales Australia 2650
    11 Lkh-Univ. Klinikum Graz Graz Austria 8036
    12 Klinikum Klagenfurt am Wörtersee; Abt.Gastroenterologie&Hepatologie,Endokrinologie Klagenfurt Austria 9020
    13 Medizinische Universität Wien; Univ.Klinik für Innere Medizin III - Gastroenterologie & Hepatologie Wien Austria 1090
    14 Imeldaziekenhuis Bonheiden Belgium 2820
    15 AZ Delta (Campus Rumbeke) Roeselare Belgium 8800
    16 Hospital Sao Rafael - HSR Salvador BA Brazil 41253-190
    17 Sociedade beneficente de senhoras Hospital Sirio Libanes Brasilia DF Brazil 70200-730
    18 Hospital do Cancer UOPECCAN; Pesquisa Clínica Cascavel PR Brazil 85806-300
    19 Hospital das Clinicas - UFRGS Porto Alegre RS Brazil 90035-903
    20 Hospital Alemao Oswaldo Cruz; Oncologia Sao Paulo SP Brazil 01327-001
    21 Gordon & Leslie Diamond Health Care Centre Vancouver British Columbia Canada V5Z 1M9
    22 McGill University Health Centre - Glen Site Montreal Quebec Canada H4A 3J1
    23 Peking Union Medical College Hospital Beijing City China 100032
    24 Cancer Hospital Chinese Academy of Medical Sciences. Beijing China 100021
    25 Beijing Cancer Hospital Beijing China 100142
    26 Affiliated Hospital of Bengbu Medical College Bengbu China 233004
    27 The First Hospital of Jilin University Changchun City China 130021
    28 West China Hospital, Sichuan University Chengdu China 610041
    29 Daping Hospital of Third Military Medical University Chongqing China 400042
    30 The Second Affiliated Hospital of Dalian Medical University Dalian China 116027
    31 Mengchao Hepatobiliary Hospital Of Fujian Medical University Fuzhou City China 350025
    32 Fujian Cancer Hospital Fuzhou China 350014
    33 Cancer Center of Guangzhou Medical University Guangzhou China 510000
    34 Sun Yet-sen University Cancer Center Guangzhou China 510060
    35 Zhujiang Hospital, Southern Medical University Guangzhou China 510280
    36 Nanfang Hospital, Southern Medical University Guangzhou China 510515
    37 Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department Hangzhou City China 310022
    38 Harbin Medical University Cancer Hospital Harbin China 150081
    39 Anhui Province Cancer Hospital Hefei China 230000
    40 Anhui Provincial Hospital Hefei China 230001
    41 The Second Affiliated Hospital of Anhui Medical University Hefei China 230601
    42 Shandong Cancer Hospital Jinan China 250117
    43 The 81st Hospital of P.L.A. Nanjing City China 210002
    44 Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School Nanjing City China 210008
    45 Zhongda Hospital Affiliated to Southeast University Nanjing China 210009
    46 Guangxi Cancer Hospital of Guangxi Medical University Nanning China 530021
    47 The First Affiliate Hospital of Guangxi Medical University Nanning China 530021
    48 Zhongshan Hospital Fudan Unvierstiy Shanghai City China 200032
    49 Huashan Hospital Affiliated to Fudan University Shanghai City China 200040
    50 Fudan University Shanghai Cancer Center Shanghai City China 200120
    51 Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China 200127
    52 The First Affiliated Hospital of China Medical University Shenyang City China 110001
    53 Shengjing Hospital of China Medical University ShenYang China 110004
    54 Tianjin Cancer Hospital Tianjin China 300060
    55 The Tumor Hospital of Xinjiang Medical University Urumqi China 830000
    56 Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology Wuhan City China 430022
    57 Renmin Hospital of Wuhan University Wuhan China 430060
    58 Zhongnan Hospital of Wuhan University Wuhan China 430071
    59 Hubei Cancer Hospital Wuhan China 430079
    60 Northern Jangsu People's Hospital Yangzhou City China 225001
    61 Clinica CIMCA San José Costa Rica 10103
    62 Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika Brno Czechia 625 00
    63 Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni Praha Czechia 140 59
    64 Hopital Jean Minoz; Oncologie Besancon France 25030
    65 Hôpital Avicenne - Groupement Hospitalier Universitaire Paris Seine St Denis; Service d'Hépatologie Bobigny Cedex France 93009
    66 Hôpital Albert Michallon La Tronche France 38700
    67 Fondation Hopital Saint Joseph; Gastro-Enterologie Marseille France 13285
    68 CHU Bordeaux - Hôpital Haut-Lévêque; Service d'Hépato-Gastroentérologie et d Oncologie digestive Pessac France 33604
    69 Hopital Robert Debre; Gastro Enterologie Reims France 51092
    70 Hopital de Pontchaillou; Service Hepato Gastro Enterologie Rennes France 35033
    71 CHU de Toulouse - Hôpital Rangueil Toulouse Cedex 09 France 31059
    72 Hopitaux de Brabois - Gastro-Entereologie Vandoeuvre-les-nancy France 54511
    73 Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I.; Onkologische Gastroenterologie Bonn Germany 53127
    74 Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I Frankfurt Germany 60590
    75 Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie Regensburg Germany 93053
    76 Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I Ulm Germany 89081
    77 Queen Mary Hospital; Dept. Of Haematology & Oncology Hong Kong Hong Kong
    78 Prince of Wales Hospital; Department of Clinical Onocology Shatin Hong Kong
    79 Ospedale Regionale Di Parma; Divisione Di Oncologia Medica Parma Emilia-Romagna Italy 43100
    80 Ospedale Maggiore Policlinico; U.O.C. di Oncologia Medica Milano Lombardia Italy 20122
    81 Asst Santi Paolo E Carlo Milano Lombardia Italy 20142
    82 Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2 Pisa Toscana Italy 56100
    83 Chiba University Hospital Chiba Japan 260-8677
    84 Ehime Prefectural Central Hospital Ehime Japan 790-0024
    85 Hiroshima University Hospital Hiroshima Japan 734-8551
    86 Sapporo Kosei General Hosopital Hokkaido Japan 060-0033
    87 Hyogo Medical University Hospital Hyogo Japan 663-8501
    88 Japanese Red Cross Society Himeji Hospital Hyogo Japan 670-8540
    89 Kanazawa University Hospital Ishikawa Japan 920-8641
    90 Yokohama City University Medical Center Kanagawa Japan 232-0024
    91 Kanagawa Cancer Center Kanagawa Japan 241-8515
    92 Kitasato University Hospital Kanagawa Japan 252-0375
    93 Kumamoto University Hospital Kumamoto Japan 860-8556
    94 Osaka Red Cross Hospital Osaka Japan 543-8555
    95 Kindai University Hospital Osaka Japan 589-8511
    96 Tokushima University Hospital Tokushima Japan 770-8503
    97 Toranomon Hospital Tokyo Japan 105-8470
    98 The University of Tokyo Hospital Tokyo Japan 113-8655
    99 Japanese Red Cross Musashino Hospital Tokyo Japan 180-8610
    100 Pusan National University Hospital Busan Korea, Republic of 49241
    101 Kyungpook National University Hospital Daegu Korea, Republic of 41944
    102 CHA Bundang Medical Center Gyeonggi-do Korea, Republic of 13496
    103 Ajou University Medical Center Gyeonggi-do Korea, Republic of 16499
    104 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    105 Seoul National University Hospital Seoul Korea, Republic of 03080
    106 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    107 Asan Medical Center Seoul Korea, Republic of 05505
    108 Gangnam Severance Hospital Seoul Korea, Republic of 06273
    109 Samsung Medical Center Seoul Korea, Republic of 06351
    110 Seoul St Mary's Hospital Seoul Korea, Republic of 06591
    111 Borame Medical Center Seoul Korea, Republic of 07061
    112 Ulsan University Hosiptal Ulsan Korea, Republic of 44033
    113 Centro Medico Dalinde Cdmx Mexico CITY (federal District) Mexico 06760
    114 Christus Muguerza Clinica Vidriera Monterrey Nuevo LEON Mexico 64570
    115 Oaxaca Site Management Organization Oaxaca Mexico 68000
    116 Maastricht University Medical Center Maastricht Netherlands 6229 HX
    117 Auckland City Hospital Auckland New Zealand 1023
    118 Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel Lima Peru 15088
    119 Instituto Nacional de Enfermedades Neoplasicas Lima Peru Lima 34
    120 Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Onkologii i Radioterapii, Warszawa Poland 02-781
    121 Group of companies "Medci" Moskva Moskovskaja Oblast Russian Federation 105229
    122 Clinical hospital #1, FBHI Volga district medical center, Federal Medical and Biological Agency Nizhny Novgorod Niznij Novgorod Russian Federation 603109
    123 First Moscow State Medical University n.a. I.M. Sechenov Moscow Russian Federation 119991
    124 Russian Scientific Center of Radiology and Surgical Technologies; Dept of Radiology St.Petersburg, Pesochny Russian Federation 197758
    125 National Cancer Centre Singapore Singapore 169610
    126 Tan Tock Seng Hospital; Oncology Singapore Singapore 308433
    127 Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain 28222
    128 Hospital Universitario Infanta Cristina; Servicio de Oncologia Badajoz Spain 06080
    129 Hospital General Universitario Gregorio Marañon; Servicio de Oncologia Madrid Spain 28007
    130 Changhua Christian Hospital Chang Hua Taiwan 500
    131 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung City Taiwan 807
    132 National Taiwan Uni Hospital; Dept of Oncology Taipei Taiwan 100
    133 Taipei Veterans General Hospital; Gastroenterology Division Taipei Taiwan 112
    134 Chang Gung Medical Foundation - Linkou; Dept. of Hepato-Gastroenterology Taoyuan Taiwan 333
    135 Rajavithi Hospital; Division of Medical Oncology Bangkok Thailand 10400
    136 Siriraj Hospital; Medical Oncology Unit Bangkok Thailand 10700
    137 Chiang Rai Prachanukroh Hospital; Department Of Medicine Chiang Rai Thailand 57000
    138 Chulabhorn Hospital; Medical Oncology Lak Si Thailand 10210
    139 Adana Baskent University Hospital; Medical Oncology Adana Turkey 01120

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04102098
    Other Study ID Numbers:
    • WO41535
    • 2019-002491-14
    First Posted:
    Sep 25, 2019
    Last Update Posted:
    Aug 23, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Recurrence
    Bevacizumab
    Atezolizumab

    Study Results

    No Results Posted as of Aug 23, 2022