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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03434379




Registration number
NCT03434379
Ethics application status
Date submitted
31/01/2018
Date registered
15/02/2018
Date last updated
24/06/2020

Titles & IDs
Public title
A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma [IMbrave150]
Scientific title
A Phase III, Open-Label, Randomized Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
Secondary ID [1] 0 0
2017-003691-31
Secondary ID [2] 0 0
YO40245
Universal Trial Number (UTN)
Trial acronym
IMbrave150
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

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

Experimental: Atezolizumab + Bevacizumab - Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator

Active Comparator: Sorafenib - Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator


Treatment: Drugs: Atezolizumab
Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21 day cycle

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21 day cycle

Treatment: Drugs: Sorafenib
Sorafenib will be administered by mouth, 400 mg twice per day, on days 1-21 of each 21-day cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization to death from any cause, through the end of study (up to approximately 4 years)
Primary outcome [2] 0 0
Progression Free Survival (PFS) as Determined by an Independent Review Facility (IRF) According to Response Evalutaion Criteria in Solid Tumors (RECIST) v1.1
Timepoint [2] 0 0
Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Secondary outcome [1] 0 0
Objective Response (OR) defined as complete response or partial response as determined by the Investigator according to RECIST V1.1
Timepoint [1] 0 0
From baseline until disease progression or death, whichever occurs first (approximately 4 years)
Secondary outcome [2] 0 0
Progression Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1
Timepoint [2] 0 0
Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 4 years)
Secondary outcome [3] 0 0
Time to Progression (TTP) as Determined by an Investigator According to RECIST v1.1
Timepoint [3] 0 0
Randomization to first occurance of disease progression (up to approximately 4 years)
Secondary outcome [4] 0 0
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Timepoint [4] 0 0
From first occurrence of a documented objective response to disease progression or death. Following initiation of study treatment, assessed at baseline, every 6 weeks for the first 54 weeks, and every 9 weeks thereafter (up to approximately 4 years)
Secondary outcome [5] 0 0
OR defined as complete or partial response as Determined by an IRF According to RECIST v1.1
Timepoint [5] 0 0
From baseline until disease progression or death, whichever occurs first (approximately 4 years)
Secondary outcome [6] 0 0
TTP as Determined by an IRF According to RECIST v1.1
Timepoint [6] 0 0
Randomization to the first occurence of disease progression through the end of study (up to approximately 4 years)
Secondary outcome [7] 0 0
DOR as Determined by an IRF According to RECIST v1.1
Timepoint [7] 0 0
From the first occurrence of a documented objective response until confirmed disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years)
Secondary outcome [8] 0 0
OR defined as complete or partial response, as Determined by an IRF According to Hepatocellular Carcinoma Modified RECIST (HCC mRECIST)
Timepoint [8] 0 0
From baseline until disease progression or death, whichever occurs first (approximately 4 years)
Secondary outcome [9] 0 0
PFS as Determined by an IRF According to HCC mRECIST
Timepoint [9] 0 0
Randomization to first occurrence of disease progression or death from any cause (whichever occurs first), through the end of study (up to approximately 4 years)
Secondary outcome [10] 0 0
TTP as Determined by an IRF According to HCC mRECIST
Timepoint [10] 0 0
Randomization to first occurrence of disease progression through the end of study (up to approximately 4 years)
Secondary outcome [11] 0 0
DOR as Determined by an IRF According to HCC mRECIST
Timepoint [11] 0 0
Time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) through the end of study (up to approximately 4 years)
Secondary outcome [12] 0 0
Time to Deterioration (TTD) in Patient-Reported GHS/QoL, physical functioning, and role functioning, as determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score
Timepoint [12] 0 0
Randomization to first deterioration maintained for two consecutive assessments, or one assessment followed by death (from any cause) within 3 weeks from any cause, through 1 year after treatment discontinuation
Secondary outcome [13] 0 0
PFS as determined by the investigator according to RECIST v1.1
Timepoint [13] 0 0
Baseline Serum Alpha-Fetoprotein (AFP) Level (< 400 ng/mL or >/=400 ng/mL)
Secondary outcome [14] 0 0
Serum Concentration of Atezolizumab
Timepoint [14] 0 0
Day 1 cycle 1, prior to infusion and 30 minutes post-infusion; Day 1 of cycles 2, 3, 4 , 8, 12 and 16 prior to infusion; at treatment discontinuation, through end of study (Approximately 4 years)
Secondary outcome [15] 0 0
Change from Baseline in Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [15] 0 0
Day 1 cycle 1, prior to infusion; Day 1 of cycles 2, 3, 4 , 8, 12 and 16 prior to infusion; at treatment discontinuation, through end of study (Approximately 4 years)
Secondary outcome [16] 0 0
Percentage of Participants with Adverse Events
Timepoint [16] 0 0
Baseline to end of study (approximately 4 years)
Secondary outcome [17] 0 0
PFS as Determined by an IRF According to RECIST v1.1
Timepoint [17] 0 0
Baseline Serum AFP Level (< 400 ng/mL or >/=400 ng/mL)
Secondary outcome [18] 0 0
OS
Timepoint [18] 0 0
Baseline Serum AFP Level (< 400 ng/mL or >/= 400 ng/mL)

Eligibility
Key inclusion criteria
- Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)

- No prior systemic therapy for HCC. Previous use of herbal therapies/traditional
Chinese medicines with anti-cancer activity included in the label is allowed, provided
that these medications are discontinued prior to randomization.

- At least one measurable untreated lesion

- ECOG Performance Status of 0 or 1

- Adequate hematologic and end-organ function

- For women of childbearing potential: agreement to remain abstinent

- For men: agreement to remain abstinent

- Child-Pugh class A
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of leptomeningeal disease

- 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 computed tomography scan

- Known active tuberculosis

- 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

- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
or within at least 5 months after the last dose of atezolizumab, 6 months after the
last dose of bevacizumab, or 1 month after the last dose of sorafenib

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

- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
high-risk for bleeding

- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
to initiation of study treatment.

- Moderate or severe ascites

- History of hepatic encephalopathy

- Co-infection of HBV and HCV

- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures

- Uncontrolled or symptomatic hypercalcemia

- Treatment with systemic immunostimulatory agents

- Inadequately controlled arterial hypertension

- Prior history of hypertensive crisis or hypertensive encephalopathy

- Evidence of bleeding diathesis or significant coagulopathy

- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction
including sub-occlusive disease related to the underlying disease or requirement for
routine parenteral hydration

- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture

- Metastatic disease that involves major airways or blood vessels, or centrally located
mediastinal tumor masses

- Local therapy to liver within 28 days prior to initiation of study treatment or
non-recovery from side effects of any such procedure

- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
St George Hospital - Kogarah
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [4] 0 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 0 0
2200 - Bankstown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment postcode(s) [4] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Mexico
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
New Brunswick
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
China
State/province [21] 0 0
Beijing City
Country [22] 0 0
China
State/province [22] 0 0
Beijing
Country [23] 0 0
China
State/province [23] 0 0
Changchun
Country [24] 0 0
China
State/province [24] 0 0
Changsha City
Country [25] 0 0
China
State/province [25] 0 0
Foshan
Country [26] 0 0
China
State/province [26] 0 0
Fuzhou
Country [27] 0 0
China
State/province [27] 0 0
Guangzhou
Country [28] 0 0
China
State/province [28] 0 0
Hangzhou
Country [29] 0 0
China
State/province [29] 0 0
Harbin
Country [30] 0 0
China
State/province [30] 0 0
Hefei
Country [31] 0 0
China
State/province [31] 0 0
Jilin City
Country [32] 0 0
China
State/province [32] 0 0
Jinan
Country [33] 0 0
China
State/province [33] 0 0
Nanjing City
Country [34] 0 0
China
State/province [34] 0 0
Shanghai
Country [35] 0 0
China
State/province [35] 0 0
Wuhan
Country [36] 0 0
Czechia
State/province [36] 0 0
Brno
Country [37] 0 0
Czechia
State/province [37] 0 0
Olomouc
Country [38] 0 0
France
State/province [38] 0 0
Lille
Country [39] 0 0
France
State/province [39] 0 0
Lyon
Country [40] 0 0
France
State/province [40] 0 0
Marseille
Country [41] 0 0
France
State/province [41] 0 0
Montpellier
Country [42] 0 0
France
State/province [42] 0 0
Nantes
Country [43] 0 0
France
State/province [43] 0 0
Nice Cedex
Country [44] 0 0
France
State/province [44] 0 0
Rouen
Country [45] 0 0
France
State/province [45] 0 0
Strasbourg
Country [46] 0 0
France
State/province [46] 0 0
Vandoeuvre-les-nancy
Country [47] 0 0
France
State/province [47] 0 0
Villejuif
Country [48] 0 0
Germany
State/province [48] 0 0
Berlin
Country [49] 0 0
Germany
State/province [49] 0 0
Frankfurt
Country [50] 0 0
Germany
State/province [50] 0 0
Freiburg
Country [51] 0 0
Germany
State/province [51] 0 0
Hamburg
Country [52] 0 0
Germany
State/province [52] 0 0
Hannover
Country [53] 0 0
Germany
State/province [53] 0 0
Leipzig
Country [54] 0 0
Germany
State/province [54] 0 0
Mainz
Country [55] 0 0
Germany
State/province [55] 0 0
Regensburg
Country [56] 0 0
Hong Kong
State/province [56] 0 0
Hong Kong
Country [57] 0 0
Hong Kong
State/province [57] 0 0
Shatin
Country [58] 0 0
Italy
State/province [58] 0 0
Campania
Country [59] 0 0
Italy
State/province [59] 0 0
Emilia-Romagna
Country [60] 0 0
Italy
State/province [60] 0 0
Piemonte
Country [61] 0 0
Italy
State/province [61] 0 0
Sardegna
Country [62] 0 0
Italy
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Toscana
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Italy
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Veneto
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Japan
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Chiba
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Japan
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Fukuoka
Country [66] 0 0
Japan
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Hokkaido
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Japan
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Ishikawa
Country [68] 0 0
Japan
State/province [68] 0 0
Kanagawa
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Japan
State/province [69] 0 0
Kumamoto
Country [70] 0 0
Japan
State/province [70] 0 0
Kyoto
Country [71] 0 0
Japan
State/province [71] 0 0
Osaka
Country [72] 0 0
Japan
State/province [72] 0 0
Saga
Country [73] 0 0
Japan
State/province [73] 0 0
Shizuoka
Country [74] 0 0
Japan
State/province [74] 0 0
Tokyo
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Daegu
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Jeollanam-do
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Seoul
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Ulsan
Country [79] 0 0
Poland
State/province [79] 0 0
Gdansk
Country [80] 0 0
Poland
State/province [80] 0 0
Myslowice
Country [81] 0 0
Poland
State/province [81] 0 0
Olsztyn
Country [82] 0 0
Poland
State/province [82] 0 0
Warszawa
Country [83] 0 0
Poland
State/province [83] 0 0
Wroclaw
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Moskovskaja Oblast
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Saint Petersburg
Country [86] 0 0
Singapore
State/province [86] 0 0
Singapore
Country [87] 0 0
Spain
State/province [87] 0 0
Cantabria
Country [88] 0 0
Spain
State/province [88] 0 0
Barcelona
Country [89] 0 0
Spain
State/province [89] 0 0
Madrid
Country [90] 0 0
Spain
State/province [90] 0 0
Zaragoza
Country [91] 0 0
Taiwan
State/province [91] 0 0
Tainan
Country [92] 0 0
Taiwan
State/province [92] 0 0
Taipei
Country [93] 0 0
Taiwan
State/province [93] 0 0
Taoyuan County
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Bristol
Country [95] 0 0
United Kingdom
State/province [95] 0 0
Glasgow
Country [96] 0 0
United Kingdom
State/province [96] 0 0
London
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the efficacy and safety of atezolizumab in combination with
bevacizumab compared with sorafenib in participants with locally advanced or metastatic
Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.
Trial website
https://clinicaltrials.gov/show/NCT03434379
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
Reference Study ID Number: YO40245 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03434379