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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04102098




Registration number
NCT04102098
Ethics application status
Date submitted
23/09/2019
Date registered
25/09/2019

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2019-002491-14
Secondary ID [2] 0 0
WO41535
Universal Trial Number (UTN)
Trial acronym
IMbrave050
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Bevacizumab

Experimental: Arm A (atezolizumab plus bevacizumab) - Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.

No intervention: Arm B (active surveillance) - Active surveillance of participants.


Treatment: Drugs: Atezolizumab
Atezolizumab 1200 mg will be administered by IV infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-Free Survival (RFS), as Determined by IRF
Timepoint [1] 0 0
Baseline up to approximately 33 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Baseline up to approximately 91 months
Secondary outcome [2] 0 0
RFS as Determined by the Investigator
Timepoint [2] 0 0
Baseline up to approximately 91 months
Secondary outcome [3] 0 0
Time to Recurrence (TTR)
Timepoint [3] 0 0
Baseline up to approximately 91 months
Secondary outcome [4] 0 0
RFS Rate at 24 and 36 Months, as Assessed by the IRF
Timepoint [4] 0 0
Randomization up to 24 months and up to 36 months
Secondary outcome [5] 0 0
RFS Rate at 24 and 36 Months, as Assessed by the Investigator
Timepoint [5] 0 0
Randomization up to 24 months and up to 36 months
Secondary outcome [6] 0 0
OS Rate at 24 and 36 Months
Timepoint [6] 0 0
Baseline to 24 and 36 months
Secondary outcome [7] 0 0
Time to Extrahepatic Spread (EHS) or Macrovascular Invasion
Timepoint [7] 0 0
Baseline up to approximately 91 months
Secondary outcome [8] 0 0
RFS in Pd-L1-High Subgroup
Timepoint [8] 0 0
Baseline up to approximately 91 months
Secondary outcome [9] 0 0
Percentage of Participants With Adverse Events
Timepoint [9] 0 0
Baseline up to approximately 91 months
Secondary outcome [10] 0 0
Serum Concentration of Atezolizumab
Timepoint [10] 0 0
Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and 30 minutes after end of atezolizumab infusion on Day 1 of Cycle 1 (each cycle is 21 days)
Secondary outcome [11] 0 0
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [11] 0 0
Prior to any drug administration up to approximately 33 month

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
16/07/2027
Actual
Sample size
Target
Accrual to date
Final
668
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2650 - Wagga Wagga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
Austria
State/province [8] 0 0
Graz
Country [9] 0 0
Austria
State/province [9] 0 0
Klagenfurt
Country [10] 0 0
Austria
State/province [10] 0 0
Wien
Country [11] 0 0
Belgium
State/province [11] 0 0
Bonheiden
Country [12] 0 0
Belgium
State/province [12] 0 0
Roeselare
Country [13] 0 0
Brazil
State/province [13] 0 0
BA
Country [14] 0 0
Brazil
State/province [14] 0 0
DF
Country [15] 0 0
Brazil
State/province [15] 0 0
PR
Country [16] 0 0
Brazil
State/province [16] 0 0
RS
Country [17] 0 0
Brazil
State/province [17] 0 0
SP
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
China
State/province [20] 0 0
Beijing City
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Bengbu
Country [23] 0 0
China
State/province [23] 0 0
Changchun City
Country [24] 0 0
China
State/province [24] 0 0
Chengdu
Country [25] 0 0
China
State/province [25] 0 0
Chongqing
Country [26] 0 0
China
State/province [26] 0 0
Dalian
Country [27] 0 0
China
State/province [27] 0 0
Fuzhou City
Country [28] 0 0
China
State/province [28] 0 0
Fuzhou
Country [29] 0 0
China
State/province [29] 0 0
Guangzhou City
Country [30] 0 0
China
State/province [30] 0 0
Guangzhou
Country [31] 0 0
China
State/province [31] 0 0
Hangzhou City
Country [32] 0 0
China
State/province [32] 0 0
Harbin
Country [33] 0 0
China
State/province [33] 0 0
Hefei City
Country [34] 0 0
China
State/province [34] 0 0
Hefei
Country [35] 0 0
China
State/province [35] 0 0
Jinan
Country [36] 0 0
China
State/province [36] 0 0
Nanjing City
Country [37] 0 0
China
State/province [37] 0 0
Nanjing
Country [38] 0 0
China
State/province [38] 0 0
Nanning City
Country [39] 0 0
China
State/province [39] 0 0
Nanning
Country [40] 0 0
China
State/province [40] 0 0
Shanghai City
Country [41] 0 0
China
State/province [41] 0 0
Shanghai
Country [42] 0 0
China
State/province [42] 0 0
Shenyang City
Country [43] 0 0
China
State/province [43] 0 0
ShenYang
Country [44] 0 0
China
State/province [44] 0 0
Tianjin
Country [45] 0 0
China
State/province [45] 0 0
Urumqi
Country [46] 0 0
China
State/province [46] 0 0
Wuhan City
Country [47] 0 0
China
State/province [47] 0 0
Wuhan
Country [48] 0 0
China
State/province [48] 0 0
Yangzhou City
Country [49] 0 0
Costa Rica
State/province [49] 0 0
San José
Country [50] 0 0
Czechia
State/province [50] 0 0
Brno
Country [51] 0 0
Czechia
State/province [51] 0 0
Praha
Country [52] 0 0
France
State/province [52] 0 0
Besancon
Country [53] 0 0
France
State/province [53] 0 0
Bobigny Cedex
Country [54] 0 0
France
State/province [54] 0 0
La Tronche
Country [55] 0 0
France
State/province [55] 0 0
Marseille
Country [56] 0 0
France
State/province [56] 0 0
Pessac
Country [57] 0 0
France
State/province [57] 0 0
Reims
Country [58] 0 0
France
State/province [58] 0 0
Rennes
Country [59] 0 0
France
State/province [59] 0 0
Toulouse Cedex 09
Country [60] 0 0
France
State/province [60] 0 0
Vandoeuvre-les-nancy
Country [61] 0 0
Germany
State/province [61] 0 0
Bonn
Country [62] 0 0
Germany
State/province [62] 0 0
Frankfurt
Country [63] 0 0
Germany
State/province [63] 0 0
Regensburg
Country [64] 0 0
Germany
State/province [64] 0 0
Ulm
Country [65] 0 0
Hong Kong
State/province [65] 0 0
Hong Kong
Country [66] 0 0
Hong Kong
State/province [66] 0 0
Shatin
Country [67] 0 0
Italy
State/province [67] 0 0
Emilia-Romagna
Country [68] 0 0
Italy
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Lombardia
Country [69] 0 0
Italy
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Toscana
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Japan
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Chiba
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Japan
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Ehime
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Japan
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Hiroshima
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Japan
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Hokkaido
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Japan
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Hyogo
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Japan
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Ishikawa
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Japan
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Kanagawa
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Japan
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Kumamoto
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Japan
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Osaka
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Japan
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Tokushima
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Japan
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Tokyo
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Korea, Republic of
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Busan
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Korea, Republic of
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Daegu
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
State/province [85] 0 0
Seoul
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Korea, Republic of
State/province [86] 0 0
Ulsan
Country [87] 0 0
Mexico
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Mexico CITY (federal District)
Country [88] 0 0
Mexico
State/province [88] 0 0
Nuevo LEON
Country [89] 0 0
Mexico
State/province [89] 0 0
Oaxaca
Country [90] 0 0
Netherlands
State/province [90] 0 0
Maastricht
Country [91] 0 0
New Zealand
State/province [91] 0 0
Auckland
Country [92] 0 0
Peru
State/province [92] 0 0
Lima
Country [93] 0 0
Poland
State/province [93] 0 0
Warszawa
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Moskovskaja Oblast
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Niznij Novgorod
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Sankt Petersburg
Country [97] 0 0
Singapore
State/province [97] 0 0
Singapore
Country [98] 0 0
Spain
State/province [98] 0 0
Madrid
Country [99] 0 0
Spain
State/province [99] 0 0
Badajoz
Country [100] 0 0
Taiwan
State/province [100] 0 0
Chang Hua
Country [101] 0 0
Taiwan
State/province [101] 0 0
Kaohsiung City
Country [102] 0 0
Taiwan
State/province [102] 0 0
Taipei
Country [103] 0 0
Taiwan
State/province [103] 0 0
Taoyuan
Country [104] 0 0
Thailand
State/province [104] 0 0
Bangkok
Country [105] 0 0
Thailand
State/province [105] 0 0
Chiang Rai
Country [106] 0 0
Thailand
State/province [106] 0 0
Lak Si
Country [107] 0 0
Turkey
State/province [107] 0 0
Adana

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04102098