Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy

Hepatocellular Carcinoma Clinical Trial

— COSMIC-312  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03755791
• Other study ID #: XL184-312
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 10, 2018
• Est. completion date: December 1, 2024

Study information

• Verified date: March 2024
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 837
• Est. completion date: December 1, 2024
• Est. primary completion date: March 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Cabozantinib
Supplied as 20-mg tablets; administered orally daily at 40 mg
• Cabozantinib
Supplied as 60-mg tablets; administered orally once daily at 60 mg
• Sorafenib
Supplied as 200-mg tablets; administered orally twice daily at 400 mg
• Atezolizumab
Supplied as 1200 mg/20 mL (60 mg/mL) in sing-dose vials; administered as an IV infusion once every 3 weeks (q3w).

Locations

Country	Name	City	State
Argentina	Exelixis Clinical Site #213	City of Buenos Aires	Buenos Aires
Argentina	Exelixis Clinical Site #216	City of Buenos Aires	Buenos Aires
Argentina	Exelixis Clinical Site #217	City of Buenos Aires	Buenos Aires
Argentina	Exelixis Clinical Site #219	Pilar	Buenos Aires
Argentina	Exelixis Clinical Site #201	Rosario	Santa Fe
Argentina	Exelixis Clinical Site #220	Rosario	Santa Fe
Australia	Exelixis Clinical Site #107	Box Hill	Victoria
Australia	Exelixis Clinical Site #78	Camperdown	New South Wales
Australia	Exelixis Clinical Site #165	Darlinghurst	New South Wales
Australia	Exelixis Clinical Site #142	Greenslopes	Queensland
Australia	Exelixis Clinical Site #166	Heidelberg	Victoria
Australia	Exelixis Clinical Site #171	Kingswood	New South Wales
Australia	Exelixis Clinical Site #126	Kogarah	New South Wales
Australia	Exelixis Clinical Site #17	Kurralta Park	South Australia
Australia	Exelixis Clinical Site #190	Nedlands	Western Australia
Australia	Exelixis Clinical Site #72	Parkville	Victoria
Australia	Exelixis Clinical Site #155	Westmead	New South Wales
Austria	Exelixis Clinical Site #198	Graz	Steiermark
Austria	Exelixis Clinical Site #150	Klagenfurt	Kärnten
Austria	Exelixis Clinical Site #64	Linz	Oberosterreich
Austria	Exelixis Clinical Site #137	St. Pölten	Lower Austria
Austria	Exelixis Clinical Site #174	Wien
Belgium	Exelixis Clinical Site #50	Brussels	California
Belgium	Exelixis Clinical Site #65	Brussels
Belgium	Exelixis Clinical Site #169	Edegem
Belgium	Exelixis Clinical Site #148	Gent
Belgium	Exelixis Clinical Site #57	Haine-Saint-Paul
Belgium	Exelixis Clinical Site #188	Leuven
Belgium	Exelixis Clinical Site #102	Liège
Brazil	Exelixis Clinical Site #175	Barretos	SP
Brazil	Exelixis Clinical Site #89	Belo Horizonte	MG
Brazil	Exelixis Clinical Site #98	Belo Horizonte	MG
Brazil	Exelixis Clinical Site #113	Curitiba	PR
Brazil	Exelixis Clinical Site #121	Jaú	SP
Brazil	Exelixis Clinical Site #203	Porto Alegre	RS
Brazil	Exelixis Clinical Site #184	Salvador	BA
Brazil	Exelixis Clinical Site #156	São Paulo	SP
Brazil	Exelixis Clinical Site #181	São Paulo	SP
Brazil	Exelixis Clinical Site #186	São Paulo	SP
Brazil	Exelixis Clinical Site #187	São Paulo	SP
Brazil	Exelixis Clinical Site #91	São Paulo
Canada	Exelixis Clinical Site #71	Calgary	Alberta
Canada	Exelixis Clinical Site #205	Edmonton	Alberta
Canada	Exelixis Clinical Site #222	Halifax	Nova Scotia
Canada	Exelixis Clinical Site #194	Hamilton	Ontario
Canada	Exelixis Clinical Site #85	Montréal	Quebec
Canada	Exelixis Clinical Site #212	Ottawa	Ontario
Canada	Exelixis Clinical Site #34	Winnipeg	Manitoba
China	Exelixis Clinical Site #237	Beijing
China	Exelixis Site #239	Beijing
China	Exelixis Clinical Site #229	Changchun	Jilin
China	Exelixis Clinical Site #246	Changchun	Jilin
China	Exelixis Clinical Site #224	Changsha	Hunan
China	Exelixis Clinical Site #231	Changsha	Hunan
China	Exelixis Site #241	Changsha	Hunan
China	Exelixis Clinical Site #235	Chengdu	Sichuan
China	Exelixis Clinical Site #228	Fuzhou	Fujian
China	Exelixis Clinical Site #242	Guangzhou	Guangdong
China	Exelixis Clinical Site #218	Hangzhou	Zhejiang
China	Exelixis Clinical Site #223	Hangzhou	Zhejiang
China	Exelixis Clinical Site #227	Harbin	Heilongjiang
China	Exelixis Clinical Site #233	Hefei	Anhui
China	Exelixis Clinical Site #234	Jiangyin	Jiansu
China	Exelixis Clinical Site #226	Linyi	Shandong
China	Exelixis Clinical Site #221	Nanchang	Jiangxi
China	Exelixis Clinical Site #238	Nanchang	Jiangxi
China	Exelixis Clinical Site #185	Nanjing	Jiangsu
China	Exelixis Clinical Site #232	Shanghai
China	Exelixis Site #240	Shanghai
China	Exelixis Clinical Site #236	Shenyang	Liaoning
China	Exelixis Clinical Site #225	Xiamen	Fujian
China	Exelixis Clinical Site #230	Zhengzhou	Henan
Colombia	Exelixis Clinical Site #130	Montería	Cordoba
Czechia	Exelixis Clinical Site #18	Hradec Králové
Czechia	Exelixis Clinical Site #37	Olomouc
Czechia	Exelixis Clinical Site #10	Praha 4
Czechia	Exelixis Clinical Site #38	Praha 5
France	Exelixis Clinical Site #43	Amiens
France	Exelixis Clinical Site #27	Besancon
France	Exelixis Clinical Site #56	Bondy Cedex
France	Exelixis Clinical Site #29	Caen Cedex 09
France	Exelixis Clinical Site #48	Clichy
France	Exelixis Clinical Site #23	Grenoble
France	Exelixis Clinical Site #55	Lille Cedex
France	Exelixis Clinical Site #16	Lyon Cedex 4
France	Exelixis Clinical Site #31	Montbeliard
France	Exelixis Clinical Site #49	Montpellier
France	Exelixis Clinical Site #47	Nantes
France	Exelixis Clinical Site #51	Nice
France	Exelixis Clinical Site #20	Pessac
France	Exelixis Clinical Site #32	Vandœuvre-lès-Nancy
Georgia	Exelixis Clinical Site #69	Batumi
Georgia	Exelixis Clinical Site #66	Tbilisi
Georgia	Exelixis Clinical Site #67	Tbilisi
Georgia	Exelixis Clinical Site #68	Tbilisi
Georgia	Exelixis Clinical Site #70	Tbilisi
Germany	Exelixis Clinical Site #214	Berlin
Germany	Exelixis Clinical Site #244	Frankfurt	Hessen
Germany	Exelixis Clinical Site #215	Hamburg
Germany	Exelixis Clinical Site #210	Kassel	Hessen
Hong Kong	Exelixis Clinical Site #146	Hong Kong
Hong Kong	Exelixis Clinical Site #42	Hong Kong
Hong Kong	Exelixis Clinical Site #9	Hong Kong
Hungary	Exelixis Clinical Site #140	Budapest
Hungary	Exelixis Clinical Site #25	Debrecen
Hungary	Exelixis Clinical Site #26	Szeged
Ireland	Exelixis Clinical Site #170	Dublin
Israel	Exelixis Clinical Site #30	Jerusalem
Israel	Exelixis Clinical Site #33	Petah Tikva
Israel	Exelixis Clinical Site #40	Ramat-Gan
Israel	Exelixis Clinical Site #35	Rehovot
Italy	Exelixis Clinical Site #158	Bologna
Italy	Exelixis Clinical Site #152	Brescia
Italy	Exelixis Clinical Site #147	Milan
Italy	Exelixis Clinical Site #149	Napoli
Italy	Exelixis Clinical Site #131	Novara
Italy	Exelixis Clinical Site #167	Roma
Italy	Exelixis Clinical Site #53	Rozzano	Milano
Italy	Exelixis Clinical Site #177	Torino
Italy	Exelixis Clinical Site #182	Torino
Italy	Exelixis Clinical Site #163	Tricase	Lecce
Italy	Exelixis Clinical Site #243	Udine
Korea, Republic of	Exelixis Clinical Site #114	Busan
Korea, Republic of	Exelixis Clinical Site #77	Busan
Korea, Republic of	Exelixis Clinical Site #86	Busan
Korea, Republic of	Exelixis Clinical Site #157	Goyang-si	Gyeonggi-do
Korea, Republic of	Exelixis Clinical Site #75	Incheon
Korea, Republic of	Exelixis Clinical Site #104	Seoul
Korea, Republic of	Exelixis Clinical Site #105	Seoul
Korea, Republic of	Exelixis Clinical Site #79	Seoul
Korea, Republic of	Exelixis Clinical Site #93	Seoul
Korea, Republic of	Exelixis Clinical Site #99	Seoul
Korea, Republic of	Exelixis Clinical Site #127	Suwon	Gyeonggi-do
Mexico	Exelixis Clinical Site #133	Ciudad De México
Mexico	Exelixis Clinical Site #135	León	Guanajuato
Mexico	Exelixis Clinical Site #160	Mexico City
Mexico	Exelixis Clinical Site #132	Monterrey	Nuevo Leon
Mexico	Exelixis Clinical Site #134	San Luis Potosí
Mexico	Exelixis Clinical Site #141	Tuxtla Gutiérrez	Chiapas
Mexico	Exelixis Clinical Site #153	Veracruz
Netherlands	Exelixis Clinical Site #52	Amsterdam	Noord-Holland
Netherlands	Exelixis Clinical Site #92	Maastricht	Limburg
Netherlands	Exelixis Clinical Site #84	Rotterdam	Zuid-Holland
Netherlands	Exelixis Clinical Site #36	Utrecht
New Zealand	Exelixis Clinical Site #60	Grafton	Auckland
New Zealand	Exelixis Clinical Site #62	Newton	Wellington
Philippines	Exelixis Clinical Site #118	Cebu City
Philippines	Exelixis Clinical Site #117	Pasig City
Philippines	Exelixis Clinical Site #136	Quezon City
Poland	Exelixis Clinical Site #24	Gdansk	Pomorskie
Poland	Exelixis Clinical Site #15	Myslowice	Slaskie
Poland	Exelixis Clinical Site #41	Warszawa	Mazowieckie
Romania	Exelixis Clinical Site #206	Bucuresti
Romania	Exelixis Clinical Site #202	Cluj-Napoca	Cluj
Romania	Exelixis Clinical Site #204	Cluj-Napoca	Cluj
Romania	Exelixis Clinical Site #211	Cluj-Napoca	Cluj
Romania	Exelixis Clinical Site #209	Iasi
Russian Federation	Exelixis Clinical Site #81	Kaluga
Russian Federation	Exelixis Clinical Site #74	Kislino	Kursk Region
Russian Federation	Exelixis Clinical Site #95	Krasnodar
Russian Federation	Exelixis Clinical Site #108	Moscow
Russian Federation	Exelixis Clinical Site #101	Murmansk
Russian Federation	Exelixis Clinical Site #80	Nizhny Novgorod
Russian Federation	Exelixis Clinical Site #111	Saint Petersburg
Russian Federation	Exelixis Clinical Site #90	Saint-Petersburg
Russian Federation	Exelixis Clinical Site #73	Sochi
Singapore	Exelixis Clinical Site #106	Singapore
Singapore	Exelixis Clinical Site #116	Singapore
Singapore	Exelixis Clinical Site #97	Singapore
Spain	Exelixis Clinical Site #103	Barcelona
Spain	Exelixis Clinical Site #164	Madrid
Spain	Exelixis Clinical Site #63	Madrid
Spain	Exelixis Clinical Site #21	Majadahonda	Madrid
Spain	Exelixis Clinical Site #22	Majadahonda	Madrid
Spain	Exelixis Clinical Site #59	Pamplona	Navarra
Spain	Exelixis Clinical Site #28	Santander	Cantabria
Spain	Exelixis Clinical Site #168	Valencia
Spain	Exelixis Clinical Site #45	Zaragoza
Switzerland	Exelixis Clinical Site #115	Basel
Switzerland	Exelixis Clinical Site #172	Bern
Switzerland	Exelixis Clinical Site #110	Saint Gallen
Switzerland	Exelixis Clinical Site #61	Zurich
Taiwan	Exelixis Clinical Site #119	Changhua
Taiwan	Exelixis Clinical Site #162	Kaohsiung
Taiwan	Exelixis Clinical Site #161	Taichung
Taiwan	Exelixis Clinical Site #145	Tainan
Taiwan	Exelixis Clinical Site #197	Tainan City
Taiwan	Exelixis Clinical Site #128	Taipei
Taiwan	Exelixis Clinical Site #82	Taipei
Taiwan	Exelixisi Clinical Site #100	Taipei
Taiwan	Exelixis Clinical Site #94	Taoyuan
Thailand	Exelixis Clinical Site #143	Chiang Mai
Thailand	Exelixis Clinical Site #139	Hat Yai	Songkla
Thailand	Exelixis Clinical Site #183	Khon Kaen
Thailand	Exelixis Clinical Site #96	Pathum Wan	Bangkok
Turkey	Exelixis Clinical Site #178	Ankara
Turkey	Exelixis Clinical Site #193	Ankara
Turkey	Exelixis Clinical Site #173	Edirne
Turkey	Exelixis Clinical Site #179	Istanbul
Turkey	Exelixis Clinical Site #189	Istanbul	Instanbul
Turkey	Exelixis Clinical Site #180	Malatya
Ukraine	Exelixis Clinical Site #125	Chernivtsi
Ukraine	Exelixis Clinical Site #122	Dnipro
Ukraine	Exelixis Clinical Site #123	Kharkiv
Ukraine	Exelixis Clinical Site #124	Odesa
Ukraine	Exelixis Clinical Site #138	Uzhhorod
United Kingdom	Exelixis Clinical Site #196	Belfast	Northern Ireland
United Kingdom	Exelixis Clinical Site #83	Bristol	England
United Kingdom	Exelixis Clinical Site #87	Cambridge	England
United Kingdom	Exelixis Clinical Site #129	London	England
United Kingdom	Exelixis Clinical Site #151	London	England
United Kingdom	Exelixis Clinical Site #192	Manchester	England
United States	Exelixis Clinical Site #76	Albuquerque	New Mexico
United States	Exelixis Clinical Site #4	Atlanta	Georgia
United States	Exelixis Clinical Site #6	Baltimore	Maryland
United States	Exelixis Clinical Site #7	Burlington	Massachusetts
United States	Exelixis Clinical Site #12	Chapel Hill	North Carolina
United States	Exelixis Clinical Site #144	Charleston	South Carolina
United States	Exelixis Clinical Site #120	Chicago	Illinois
United States	Exelixis Clinical Site #195	Chicago	Illinois
United States	Exelixis Clinical Site #199	Dallas	Texas
United States	Exelixis Clinical Site #154	Houston	Texas
United States	Exelixis Clinical Site #11	Kansas City	Missouri
United States	Exelixis Clinical Site #5	Kansas City	Missouri
United States	Exelixis Clinical Site #44	La Jolla	California
United States	Exelixis Clinical Site #1	Las Vegas	Nevada
United States	Exelixis Clinical Site #112	Los Angeles	California
United States	Exelixis Clinical Site #191	Miami	Florida
United States	Exelixis Clinical Site #14	New Brunswick	New Jersey
United States	Exelixis Clinical Site #200	Orange	California
United States	Exelixis Clinical Site #88	Philadelphia	Pennsylvania
United States	Exelixis Clinical Site #208	Phoenix	Arizona
United States	Exelixis Clinical Site #176	Portland	Oregon
United States	Exelixis Clinical Site #2	Rialto	California
United States	Exelixis Clinical Site #8	Saint Louis	Missouri
United States	Exelixis Clinical Site #207	San Diego	California
United States	Exelixis Clinical Site #109	San Francisco	California
United States	Exelixis Clinical Site #54	San Francisco	California
United States	Exelixis Clinical Site #13	Seattle	Washington
United States	Exelixis Clinical Site #46	Seattle	Washington
United States	Exelixis Clinical Site #3	Spokane	Washington
United States	Exelixis Clinical Site #19	Temple	Texas
United States	Exelixis Clinical Site #39	Toledo	Ohio
United States	Exelixis Clinical Site #159	Tucson	Arizona
United States	Exelixis Clinical Site #58	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Colombia,  Czechia,  France,  Georgia,  Germany,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Philippines,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm	Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)	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	Duration of Overall Survival (OS) for the experimental arm vs. the control arm		Up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause.
Secondary	Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm	Duration of PFS per RECIST 1.1 by BIRC	Up to 20 months after the first subject is randomized.