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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02576509




Registration number
NCT02576509
Ethics application status
Date submitted
13/10/2015
Date registered
15/10/2015
Date last updated
19/03/2024

Titles & IDs
Public title
An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma
Scientific title
A Randomized, Multi-center Phase III Study of Nivolumab Versus Sorafenib as First-Line Treatment in Patients With Advanced Hepatocellular Carcinoma (CheckMate 459: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 459)
Secondary ID [1] 0 0
CA209-459
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 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 - Nivolumab
Treatment: Drugs - Sorafenib

Experimental: Nivolumab - Nivolumab specified dose on specified days

Active comparator: Sorafenib - Sorafenib specified dose on specified days


Treatment: Drugs: Nivolumab
Specified Dose on Specified Days

Treatment: Drugs: Sorafenib
Specified Dose on Specified Days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Assessment method [1] 0 0
OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates. Based on Kaplan-Meier Estimates.
Timepoint [1] 0 0
time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per BICR RECIST 1.1
Assessment method [1] 0 0
ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later. Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors
Timepoint [1] 0 0
the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
Secondary outcome [2] 0 0
Progression-Free Survival (PFS)
Assessment method [2] 0 0
PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.
Timepoint [2] 0 0
time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months)
Secondary outcome [3] 0 0
Efficacy Based on PD-L1 Expression - OS and PFS
Assessment method [3] 0 0
PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: * PD-L1 \> X %: = X % PD-L1 expression * PD-L1 \< X %: \< X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.
Timepoint [3] 0 0
the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)
Secondary outcome [4] 0 0
Efficacy Based on PD-L1 Expression - ORR
Assessment method [4] 0 0
PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: * PD-L1 \> X %: = X % PD-L1 expression * PD-L1 \< X %: \< X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.
Timepoint [4] 0 0
the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)

Eligibility
Key inclusion criteria
* Histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
* Locoregional therapy for hepatocellular carcinoma (HCC) must be completed at least 4 weeks prior to the baseline scan
* Child-Pugh Class A
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
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
* Prior liver transplant
* Active, known, or suspected autoimmune disease

Other protocol-defined inclusion/exclusion criteria apply

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/02/2024
Sample size
Target
Accrual to date
Final
743
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - 0005 - Camperdown
Recruitment hospital [2] 0 0
Local Institution - 0007 - Adelaide
Recruitment hospital [3] 0 0
Local Institution - 0001 - Clayton
Recruitment hospital [4] 0 0
Local Institution - 0002 - Heidelberg
Recruitment hospital [5] 0 0
Local Institution - 0003 - Prahran
Recruitment hospital [6] 0 0
Local Institution - 0008 - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3181 - Prahran
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
Austria
State/province [11] 0 0
Graz
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Belgium
State/province [15] 0 0
Liege
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
China
State/province [19] 0 0
Anhui
Country [20] 0 0
China
State/province [20] 0 0
Beijing
Country [21] 0 0
China
State/province [21] 0 0
Fujian
Country [22] 0 0
China
State/province [22] 0 0
Guangdong
Country [23] 0 0
China
State/province [23] 0 0
Guangxi
Country [24] 0 0
China
State/province [24] 0 0
Heilongjiang
Country [25] 0 0
China
State/province [25] 0 0
Hunan
Country [26] 0 0
China
State/province [26] 0 0
Jiangsu
Country [27] 0 0
China
State/province [27] 0 0
Jilin
Country [28] 0 0
China
State/province [28] 0 0
Liaoning
Country [29] 0 0
China
State/province [29] 0 0
Shan3xi
Country [30] 0 0
China
State/province [30] 0 0
Shanghai
Country [31] 0 0
China
State/province [31] 0 0
Tianjin
Country [32] 0 0
China
State/province [32] 0 0
Zhejiang
Country [33] 0 0
Czechia
State/province [33] 0 0
Brno
Country [34] 0 0
Czechia
State/province [34] 0 0
Hradec Kralove
Country [35] 0 0
Czechia
State/province [35] 0 0
Olomouc
Country [36] 0 0
France
State/province [36] 0 0
La Tronche
Country [37] 0 0
France
State/province [37] 0 0
Lille Cedex
Country [38] 0 0
France
State/province [38] 0 0
Lyon
Country [39] 0 0
France
State/province [39] 0 0
Montpellier Cedex
Country [40] 0 0
France
State/province [40] 0 0
Paris Cedex 13
Country [41] 0 0
France
State/province [41] 0 0
Pessac
Country [42] 0 0
France
State/province [42] 0 0
Rennes Cedex
Country [43] 0 0
France
State/province [43] 0 0
Toulouse Cedex 9
Country [44] 0 0
Germany
State/province [44] 0 0
Berlin
Country [45] 0 0
Germany
State/province [45] 0 0
Essen
Country [46] 0 0
Germany
State/province [46] 0 0
Frankfurt
Country [47] 0 0
Germany
State/province [47] 0 0
Hamburg
Country [48] 0 0
Germany
State/province [48] 0 0
Leipzig
Country [49] 0 0
Germany
State/province [49] 0 0
Mainz
Country [50] 0 0
Germany
State/province [50] 0 0
Munich
Country [51] 0 0
Germany
State/province [51] 0 0
Regensburg
Country [52] 0 0
Germany
State/province [52] 0 0
Tuebingen
Country [53] 0 0
Hong Kong
State/province [53] 0 0
Hong Kong
Country [54] 0 0
Israel
State/province [54] 0 0
Haifa
Country [55] 0 0
Israel
State/province [55] 0 0
Jerusalem
Country [56] 0 0
Israel
State/province [56] 0 0
Petah-tikva
Country [57] 0 0
Israel
State/province [57] 0 0
Tel Aviv
Country [58] 0 0
Italy
State/province [58] 0 0
Benevento
Country [59] 0 0
Italy
State/province [59] 0 0
Bergamo
Country [60] 0 0
Italy
State/province [60] 0 0
Milan
Country [61] 0 0
Italy
State/province [61] 0 0
Orbassano
Country [62] 0 0
Italy
State/province [62] 0 0
Siena
Country [63] 0 0
Japan
State/province [63] 0 0
Chiba
Country [64] 0 0
Japan
State/province [64] 0 0
Ehime
Country [65] 0 0
Japan
State/province [65] 0 0
Fukuoka
Country [66] 0 0
Japan
State/province [66] 0 0
Gifu
Country [67] 0 0
Japan
State/province [67] 0 0
Hokkaido
Country [68] 0 0
Japan
State/province [68] 0 0
Ishikawa
Country [69] 0 0
Japan
State/province [69] 0 0
Kanagawa
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
Tokyo
Country [74] 0 0
Japan
State/province [74] 0 0
Hiroshima
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Seocho-gu
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Daegu
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Goyang-si
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Jeollanam-do
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Seoul-si
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Seoul
Country [81] 0 0
Poland
State/province [81] 0 0
Gdansk
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
Moscow
Country [85] 0 0
Singapore
State/province [85] 0 0
Singapore
Country [86] 0 0
Spain
State/province [86] 0 0
Alicante
Country [87] 0 0
Spain
State/province [87] 0 0
Majadahonda - Madrid
Country [88] 0 0
Spain
State/province [88] 0 0
Pamplona
Country [89] 0 0
Spain
State/province [89] 0 0
Santiago Compostela
Country [90] 0 0
Sweden
State/province [90] 0 0
Goteborg
Country [91] 0 0
Sweden
State/province [91] 0 0
Stockholm
Country [92] 0 0
Switzerland
State/province [92] 0 0
Basel
Country [93] 0 0
Switzerland
State/province [93] 0 0
Bern
Country [94] 0 0
Taiwan
State/province [94] 0 0
Kaohsiung County
Country [95] 0 0
Taiwan
State/province [95] 0 0
Taichung
Country [96] 0 0
Taiwan
State/province [96] 0 0
Tainan
Country [97] 0 0
Taiwan
State/province [97] 0 0
Taipei
Country [98] 0 0
Taiwan
State/province [98] 0 0
Taoyuan County
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Greater London
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Lanarkshire
Country [101] 0 0
United Kingdom
State/province [101] 0 0
Liverpool

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Ono Pharmaceutical Co. Ltd
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Bristol Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


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/NCT02576509