Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03755791




Registration number
NCT03755791
Ethics application status
Date submitted
26/11/2018
Date registered
28/11/2018
Date last updated
22/03/2024

Titles & IDs
Public title
Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy
Scientific title
A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy
Secondary ID [1] 0 0
XL184-312
Universal Trial Number (UTN)
Trial acronym
COSMIC-312
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 - Cabozantinib
Treatment: Drugs - Cabozantinib
Treatment: Drugs - Sorafenib
Treatment: Drugs - Atezolizumab

Experimental: Experimental arm - Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w

Active comparator: Control arm - Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)

Other: Single-Agent Cabozantinib arm - Subjects with advanced HCC will receive cabozantinib 60 mg qd


Treatment: Drugs: Cabozantinib
Supplied as 20-mg tablets; administered orally daily at 40 mg

Treatment: Drugs: Cabozantinib
Supplied as 60-mg tablets; administered orally once daily at 60 mg

Treatment: Drugs: Sorafenib
Supplied as 200-mg tablets; administered orally twice daily at 400 mg

Treatment: Drugs: Atezolizumab
Supplied as 1200 mg/20 mL (60 mg/mL) in sing-dose vials; administered as an IV infusion once every 3 weeks (q3w).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm
Timepoint [1] 0 0
Up to 27 months after the first subject is randomized. Defined as time from randomization to the earlier of progressive disease (PD) per RECIST 1.1 as determined by the Blinded Independent Radiology Committee (BIRC) or death from any cause.
Primary outcome [2] 0 0
Duration of Overall Survival (OS) for the experimental arm vs. the control arm
Timepoint [2] 0 0
Up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause.
Secondary outcome [1] 0 0
Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm
Timepoint [1] 0 0
Up to 20 months after the first subject is randomized.

Eligibility
Key inclusion criteria
* Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by CT or MRI per the AASLD 2018 or EASL 2018 guidelines.
* The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
* Measurable disease per RECIST 1.1 as determined by the Investigator.
* Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.
* Child-Pugh Score of A.
* Eastern Cooperative Oncology Group (ECOG) performance status of 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 carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
* Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and immune checkpoint inhibitors (ICIs). Subjects who have received local intratumoral or arterial chemotherapy are eligible; local anticancer therapy within = 28 days before randomization
* Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 8 weeks prior to randomization.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to randomization.
* Concomitant anticoagulation with oral anticoagulants

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
10/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
837
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Exelixis Clinical Site #78 - Camperdown
Recruitment hospital [2] 0 0
Exelixis Clinical Site #165 - Darlinghurst
Recruitment hospital [3] 0 0
Exelixis Clinical Site #171 - Kingswood
Recruitment hospital [4] 0 0
Exelixis Clinical Site #126 - Kogarah
Recruitment hospital [5] 0 0
Exelixis Clinical Site #155 - Westmead
Recruitment hospital [6] 0 0
Exelixis Clinical Site #142 - Greenslopes
Recruitment hospital [7] 0 0
Exelixis Clinical Site #17 - Kurralta Park
Recruitment hospital [8] 0 0
Exelixis Clinical Site #107 - Box Hill
Recruitment hospital [9] 0 0
Exelixis Clinical Site #166 - Heidelberg
Recruitment hospital [10] 0 0
Exelixis Clinical Site #72 - Parkville
Recruitment hospital [11] 0 0
Exelixis Clinical Site #190 - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2747 - Kingswood
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
4120 - Greenslopes
Recruitment postcode(s) [7] 0 0
- Kurralta Park
Recruitment postcode(s) [8] 0 0
3128 - Box Hill
Recruitment postcode(s) [9] 0 0
3084 - Heidelberg
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
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
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
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
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New Mexico
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Argentina
State/province [20] 0 0
Buenos Aires
Country [21] 0 0
Argentina
State/province [21] 0 0
Santa Fe
Country [22] 0 0
Austria
State/province [22] 0 0
Kärnten
Country [23] 0 0
Austria
State/province [23] 0 0
Lower Austria
Country [24] 0 0
Austria
State/province [24] 0 0
Oberosterreich
Country [25] 0 0
Austria
State/province [25] 0 0
Steiermark
Country [26] 0 0
Austria
State/province [26] 0 0
Wien
Country [27] 0 0
Belgium
State/province [27] 0 0
California
Country [28] 0 0
Belgium
State/province [28] 0 0
Brussels
Country [29] 0 0
Belgium
State/province [29] 0 0
Edegem
Country [30] 0 0
Belgium
State/province [30] 0 0
Gent
Country [31] 0 0
Belgium
State/province [31] 0 0
Haine-Saint-Paul
Country [32] 0 0
Belgium
State/province [32] 0 0
Leuven
Country [33] 0 0
Belgium
State/province [33] 0 0
Liège
Country [34] 0 0
Brazil
State/province [34] 0 0
BA
Country [35] 0 0
Brazil
State/province [35] 0 0
MG
Country [36] 0 0
Brazil
State/province [36] 0 0
PR
Country [37] 0 0
Brazil
State/province [37] 0 0
RS
Country [38] 0 0
Brazil
State/province [38] 0 0
SP
Country [39] 0 0
Brazil
State/province [39] 0 0
São Paulo
Country [40] 0 0
Canada
State/province [40] 0 0
Alberta
Country [41] 0 0
Canada
State/province [41] 0 0
Manitoba
Country [42] 0 0
Canada
State/province [42] 0 0
Nova Scotia
Country [43] 0 0
Canada
State/province [43] 0 0
Ontario
Country [44] 0 0
Canada
State/province [44] 0 0
Quebec
Country [45] 0 0
China
State/province [45] 0 0
Anhui
Country [46] 0 0
China
State/province [46] 0 0
Fujian
Country [47] 0 0
China
State/province [47] 0 0
Guangdong
Country [48] 0 0
China
State/province [48] 0 0
Heilongjiang
Country [49] 0 0
China
State/province [49] 0 0
Henan
Country [50] 0 0
China
State/province [50] 0 0
Hunan
Country [51] 0 0
China
State/province [51] 0 0
Jiangsu
Country [52] 0 0
China
State/province [52] 0 0
Jiangxi
Country [53] 0 0
China
State/province [53] 0 0
Jiansu
Country [54] 0 0
China
State/province [54] 0 0
Jilin
Country [55] 0 0
China
State/province [55] 0 0
Liaoning
Country [56] 0 0
China
State/province [56] 0 0
Shandong
Country [57] 0 0
China
State/province [57] 0 0
Sichuan
Country [58] 0 0
China
State/province [58] 0 0
Zhejiang
Country [59] 0 0
China
State/province [59] 0 0
Beijing
Country [60] 0 0
China
State/province [60] 0 0
Shanghai
Country [61] 0 0
Colombia
State/province [61] 0 0
Cordoba
Country [62] 0 0
Czechia
State/province [62] 0 0
Hradec Králové
Country [63] 0 0
Czechia
State/province [63] 0 0
Olomouc
Country [64] 0 0
Czechia
State/province [64] 0 0
Praha 4
Country [65] 0 0
Czechia
State/province [65] 0 0
Praha 5
Country [66] 0 0
France
State/province [66] 0 0
Amiens
Country [67] 0 0
France
State/province [67] 0 0
Besancon
Country [68] 0 0
France
State/province [68] 0 0
Bondy Cedex
Country [69] 0 0
France
State/province [69] 0 0
Caen Cedex 09
Country [70] 0 0
France
State/province [70] 0 0
Clichy
Country [71] 0 0
France
State/province [71] 0 0
Grenoble
Country [72] 0 0
France
State/province [72] 0 0
Lille Cedex
Country [73] 0 0
France
State/province [73] 0 0
Lyon Cedex 4
Country [74] 0 0
France
State/province [74] 0 0
Montbeliard
Country [75] 0 0
France
State/province [75] 0 0
Montpellier
Country [76] 0 0
France
State/province [76] 0 0
Nantes
Country [77] 0 0
France
State/province [77] 0 0
Nice
Country [78] 0 0
France
State/province [78] 0 0
Pessac
Country [79] 0 0
France
State/province [79] 0 0
Vandœuvre-lès-Nancy
Country [80] 0 0
Georgia
State/province [80] 0 0
Batumi
Country [81] 0 0
Georgia
State/province [81] 0 0
Tbilisi
Country [82] 0 0
Germany
State/province [82] 0 0
Hessen
Country [83] 0 0
Germany
State/province [83] 0 0
Berlin
Country [84] 0 0
Germany
State/province [84] 0 0
Hamburg
Country [85] 0 0
Hong Kong
State/province [85] 0 0
Hong Kong
Country [86] 0 0
Hungary
State/province [86] 0 0
Budapest
Country [87] 0 0
Hungary
State/province [87] 0 0
Debrecen
Country [88] 0 0
Hungary
State/province [88] 0 0
Szeged
Country [89] 0 0
Ireland
State/province [89] 0 0
Dublin
Country [90] 0 0
Israel
State/province [90] 0 0
Jerusalem
Country [91] 0 0
Israel
State/province [91] 0 0
Petah Tikva
Country [92] 0 0
Israel
State/province [92] 0 0
Ramat-Gan
Country [93] 0 0
Israel
State/province [93] 0 0
Rehovot
Country [94] 0 0
Italy
State/province [94] 0 0
Lecce
Country [95] 0 0
Italy
State/province [95] 0 0
Milano
Country [96] 0 0
Italy
State/province [96] 0 0
Bologna
Country [97] 0 0
Italy
State/province [97] 0 0
Brescia
Country [98] 0 0
Italy
State/province [98] 0 0
Milan
Country [99] 0 0
Italy
State/province [99] 0 0
Napoli
Country [100] 0 0
Italy
State/province [100] 0 0
Novara
Country [101] 0 0
Italy
State/province [101] 0 0
Roma
Country [102] 0 0
Italy
State/province [102] 0 0
Torino
Country [103] 0 0
Italy
State/province [103] 0 0
Udine
Country [104] 0 0
Korea, Republic of
State/province [104] 0 0
Gyeonggi-do
Country [105] 0 0
Korea, Republic of
State/province [105] 0 0
Busan
Country [106] 0 0
Korea, Republic of
State/province [106] 0 0
Incheon
Country [107] 0 0
Korea, Republic of
State/province [107] 0 0
Seoul
Country [108] 0 0
Mexico
State/province [108] 0 0
Chiapas
Country [109] 0 0
Mexico
State/province [109] 0 0
Guanajuato
Country [110] 0 0
Mexico
State/province [110] 0 0
Nuevo Leon
Country [111] 0 0
Mexico
State/province [111] 0 0
Ciudad De México
Country [112] 0 0
Mexico
State/province [112] 0 0
Mexico City
Country [113] 0 0
Mexico
State/province [113] 0 0
San Luis Potosí
Country [114] 0 0
Mexico
State/province [114] 0 0
Veracruz
Country [115] 0 0
Netherlands
State/province [115] 0 0
Limburg
Country [116] 0 0
Netherlands
State/province [116] 0 0
Noord-Holland
Country [117] 0 0
Netherlands
State/province [117] 0 0
Zuid-Holland
Country [118] 0 0
Netherlands
State/province [118] 0 0
Utrecht
Country [119] 0 0
New Zealand
State/province [119] 0 0
Auckland
Country [120] 0 0
New Zealand
State/province [120] 0 0
Wellington
Country [121] 0 0
Philippines
State/province [121] 0 0
Cebu City
Country [122] 0 0
Philippines
State/province [122] 0 0
Pasig City
Country [123] 0 0
Philippines
State/province [123] 0 0
Quezon City
Country [124] 0 0
Poland
State/province [124] 0 0
Mazowieckie
Country [125] 0 0
Poland
State/province [125] 0 0
Pomorskie
Country [126] 0 0
Poland
State/province [126] 0 0
Slaskie
Country [127] 0 0
Romania
State/province [127] 0 0
Cluj
Country [128] 0 0
Romania
State/province [128] 0 0
Bucuresti
Country [129] 0 0
Romania
State/province [129] 0 0
Iasi
Country [130] 0 0
Russian Federation
State/province [130] 0 0
Kursk Region
Country [131] 0 0
Russian Federation
State/province [131] 0 0
Kaluga
Country [132] 0 0
Russian Federation
State/province [132] 0 0
Krasnodar
Country [133] 0 0
Russian Federation
State/province [133] 0 0
Moscow
Country [134] 0 0
Russian Federation
State/province [134] 0 0
Murmansk
Country [135] 0 0
Russian Federation
State/province [135] 0 0
Nizhny Novgorod
Country [136] 0 0
Russian Federation
State/province [136] 0 0
Saint Petersburg
Country [137] 0 0
Russian Federation
State/province [137] 0 0
Saint-Petersburg
Country [138] 0 0
Russian Federation
State/province [138] 0 0
Sochi
Country [139] 0 0
Singapore
State/province [139] 0 0
Singapore
Country [140] 0 0
Spain
State/province [140] 0 0
Cantabria
Country [141] 0 0
Spain
State/province [141] 0 0
Madrid
Country [142] 0 0
Spain
State/province [142] 0 0
Navarra
Country [143] 0 0
Spain
State/province [143] 0 0
Barcelona
Country [144] 0 0
Spain
State/province [144] 0 0
Valencia
Country [145] 0 0
Spain
State/province [145] 0 0
Zaragoza
Country [146] 0 0
Switzerland
State/province [146] 0 0
Basel
Country [147] 0 0
Switzerland
State/province [147] 0 0
Bern
Country [148] 0 0
Switzerland
State/province [148] 0 0
Saint Gallen
Country [149] 0 0
Switzerland
State/province [149] 0 0
Zurich
Country [150] 0 0
Taiwan
State/province [150] 0 0
Changhua
Country [151] 0 0
Taiwan
State/province [151] 0 0
Kaohsiung
Country [152] 0 0
Taiwan
State/province [152] 0 0
Taichung
Country [153] 0 0
Taiwan
State/province [153] 0 0
Tainan City
Country [154] 0 0
Taiwan
State/province [154] 0 0
Tainan
Country [155] 0 0
Taiwan
State/province [155] 0 0
Taipei
Country [156] 0 0
Taiwan
State/province [156] 0 0
Taoyuan
Country [157] 0 0
Thailand
State/province [157] 0 0
Bangkok
Country [158] 0 0
Thailand
State/province [158] 0 0
Songkla
Country [159] 0 0
Thailand
State/province [159] 0 0
Chiang Mai
Country [160] 0 0
Thailand
State/province [160] 0 0
Khon Kaen
Country [161] 0 0
Turkey
State/province [161] 0 0
Instanbul
Country [162] 0 0
Turkey
State/province [162] 0 0
Ankara
Country [163] 0 0
Turkey
State/province [163] 0 0
Edirne
Country [164] 0 0
Turkey
State/province [164] 0 0
Istanbul
Country [165] 0 0
Turkey
State/province [165] 0 0
Malatya
Country [166] 0 0
Ukraine
State/province [166] 0 0
Chernivtsi
Country [167] 0 0
Ukraine
State/province [167] 0 0
Dnipro
Country [168] 0 0
Ukraine
State/province [168] 0 0
Kharkiv
Country [169] 0 0
Ukraine
State/province [169] 0 0
Odesa
Country [170] 0 0
Ukraine
State/province [170] 0 0
Uzhhorod
Country [171] 0 0
United Kingdom
State/province [171] 0 0
England
Country [172] 0 0
United Kingdom
State/province [172] 0 0
Northern Ireland

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 3 study evaluates the safety and efficacy of cabozantinib in combination with atezolizumab versus the standard of care sorafenib in adults with advanced hepatocellular carcinoma (HCC) who have not received previous systemic anticancer therapy. A single-agent cabozantinib arm will be enrolled in which subjects receive single agent cabozantinib in order to determine its contribution to the overall safety and efficacy of the combination with atezolizumab.
Trial website
https://clinicaltrials.gov/study/NCT03755791
Trial related presentations / publications
Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, Chan SL, Melkadze T, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Rangel JDG, Ryoo BY, Makharadze T, Merle P, Benzaghou F, Banerjee K, Hazra S, Fawcett J, Yau T. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Aug;23(8):995-1008. doi: 10.1016/S1470-2045(22)00326-6. Epub 2022 Jul 4.
Kelley RK, W Oliver J, Hazra S, Benzaghou F, Yau T, Cheng AL, Rimassa L. Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase III study design. Future Oncol. 2020 Jul;16(21):1525-1536. doi: 10.2217/fon-2020-0283. Epub 2020 Jun 3.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03755791