NCT03764293

Brief Summary

This is a randomized, open-label, international, multi-center, phase III trial to evaluate the efficacy and safety of SHR-1210 plus apatinib mesylate versus sorafenib as first-line therapy in patients with advanced HCC.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
543

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jun 2019

Typical duration for phase_3

Geographic Reach
13 countries

121 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 28, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

December 5, 2018

Completed
6 months until next milestone

Study Start

First participant enrolled

June 10, 2019

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 8, 2022

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 14, 2023

Completed
8 months until next milestone

Results Posted

Study results publicly available

February 6, 2024

Completed
Last Updated

February 6, 2024

Status Verified

February 1, 2023

Enrollment Period

2.7 years

First QC Date

November 28, 2018

Results QC Date

November 10, 2023

Last Update Submit

February 5, 2024

Conditions

Outcome Measures

Primary Outcomes (2)

  • Overall Survival (OS)

    OS was defined as the time from randomization to death from any cause.

    Up to approximately 3 years

  • Progression-free Survival (PFS) Evaluated by the Blinded Independent Review Committee (BIRC) Based on RECIST v1.1

    PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) by tumor image evaluation or death from any cause whichever occurs first as determined by BIRC according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions and the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm), or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Up to approximately 3 years

Secondary Outcomes (3)

  • Objective Response Rate (ORR)

    Up to approximately 3 years

  • Disease Control Rate (DCR)

    Up to approximately 3 years

  • Duration of Response (DOR)

    Up to approximately 3 years

Study Arms (2)

SHR-1210

EXPERIMENTAL

SHR-1210+Apatinib

Drug: SHR-1210Drug: Apatinib

Control

ACTIVE COMPARATOR

Sorafenib

Drug: Sorafenib

Interventions

Subjects receive SHR-1210 intravenously, Dosage form: lyophilised powder, Strength: 200 mg /vial

Also known as: Camrelizumab
SHR-1210

Subjects receive Apatinib orally, Dosage form: tablet, Strength: 250 mg/tablet

Also known as: Rivoceranib
SHR-1210

Subjects receive Sorafenib orally, Dosage form: tablet, Strength: 0.2 g/tablet

Control

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histopathologically or cytologically confirmed advanced HCC
  • No previous systematic treatment for HCC
  • Have at least one measurable lesion (in accordance with RECIST v1.1)
  • BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed following surgical and/or local therapy
  • ECOG-PS score 0 or 1
  • Child-Pugh Class: Grade A
  • Life Expectancy of at least 12 weeks
  • Subjects with HBV infection: HBV DNA\<500 IU/ml or \< 2500 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study
  • Subjects with HCV-RNA(+) must receive antiviral therapy
  • Adequate organ function

You may not qualify if:

  • Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma; other active malignant tumor except HCC within 5 years or simultaneously
  • Moderate-to-severe ascites with clinical symptoms
  • History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage
  • Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment
  • Known genetic or acquired hemorrhage or thrombotic tendency
  • Thrombosis or thromboembolic event within 6 months prior to the start of study treatment
  • Cardiac clinical symptom or disease that is not well controlled
  • Hypertension that can not be well controlled through antihypertensive drugs
  • Factors to affect oral administration
  • History of hepatic encephalopathy
  • Previous or current presence of metastasis to central nervous system
  • HIV infection
  • Combined hepatitis B and hepatitis C co-infection
  • Be ready for or previously received organ or allogenic bone marrow transplantation
  • Interstitial lung disease that is symptomatic or may interfere with the detection and management of suspected drug-related pulmonary toxicity
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (121)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

University of California San Diego (UCSD)-Moores Cancer Center

La Jolla, California, 92037, United States

Location

University of California - Irvine

Orange, California, 92868, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Cornell University Weill Cornell Medical College

New York, New York, 10065, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZA

Edegem, 2650, Belgium

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

Anhui Provincal Cancer Hospital

Hefei, Anhui, 230000, China

Location

Anhui Provincal Hospital

Hefei, Anhui, 230000, China

Location

The First Affiliated Hospital Of Anhui Medical University

Hefei, Anhui, 230009, China

Location

The Second Affiliated Hospital Of Anhui Medical University

Hefei, Anhui, 230601, China

Location

Chinese Academy of Medical Sciences Cancer Hospital

Beijing, Beijing Municipality, 100020, China

Location

Beijing cancer Hospital

Beijing, Beijing Municipality, 100089, China

Location

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

Location

The Second Hospital Affiliated To AMU

Chongqing, Chongqing Municipality, 400037, China

Location

The First Hospital Affiliated To AMU

Chongqing, Chongqing Municipality, 400038, China

Location

TheThird Affiliated Hospital ,Army Medical University

Chongqing, Chongqing Municipality, 400042, China

Location

The Second Affiliated Hospital of ChongQing Medical University

Chongqing, Chongqing Municipality, 400060, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

The 940th Hospital of the joint logistic support force of People's Liberation Army

Lanzhou, Gansu, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510220, China

Location

NanFang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

The first affiliated hospital of guangxi medical university

Nanning, Guangxi, 530021, China

Location

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050011, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology

Wuhan, Hubei, 430022, China

Location

Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology

Wuhan, Hubei, 430030, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410006, China

Location

Eastern Theater General Hospital, Qinhuai District Medical Area

Nanjing, Jiangsu, 210002, China

Location

The First Affiliated Hospital Of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130000, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

The Sixth People's Hospital of Shengyang

Shengyang, Liaoning, 110006, China

Location

Liaoning Cancer Hospital

Shenyang, Liaoning, 110042, China

Location

Shandong Cancer Hospital Affiliated to Shandong University

Jinan, Shandong, 250000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai Changhai Hospital

Shanghai, Shanghai Municipality, 200043, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Sichuan Cancer Hospital&Institute

Chengdu, Sichuan, 610054, China

Location

Sir Run Run Shaw Hospital

Hangzhou, Zhejiang, 310016, China

Location

ZheJiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

Location

Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin

Berlin, 13353, Germany

Location

Pamela Youde Nethersole Eastern Hospital

Hong Kong, Hong Kong

Location

The University of Hong Kong

Hong Kong, Hong Kong

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

The Chinese University of Hong Kong

Shatin, Hong Kong

Location

A.S.L. Napoli 1 Centro Ospedale del Mare

Ponticelli, Napoli, 80147, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, 25123, Italy

Location

Azienda Ospedaliero-Universitaria

Cagliari, 09124, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50134, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, 37134, Italy

Location

Centrum Medyczne Pratia Gdynia

Gdynia, 81338, Poland

Location

Centrum Onkologii-Instytut im.M.Sklodowskiej Curie

Gliwice, 44101, Poland

Location

Pratia MCM Krakow

Krakow, 30510, Poland

Location

Przychodnia Med-Polonia Sp. z o.o.

Poznan, 60693, Poland

Location

Wielkopolskie Centrum Onkologii

Poznan, 61866, Poland

Location

Centrum Zdrowia MDM

Warsaw, 00635, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, 02034, Poland

Location

NZOZ Centrum Badan Klinicznych

Wroclaw, 51162, Poland

Location

SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"

Arkhangelsk, 164045, Russia

Location

SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine

Chelyabinsk, 454087, Russia

Location

Irkutsk Regional Oncology Dispensary

Irkutsk, 664035, Russia

Location

SBIH " Clinical Oncological Dispensary # 1"

Krasnodar, 350040, Russia

Location

RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee

Kursk, 305035, Russia

Location

"VitaMed" LLC

Moscow, 121309, Russia

Location

SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare departement

Moscow, 143423, Russia

Location

CJSC Avicenna

Novosibirsk, 630099, Russia

Location

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, 644013, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

SPb SBIH "City Clinical Oncological Dispensary"

Saint Petersburg, 197022, Russia

Location

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint Petersburg, 197758, Russia

Location

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, 450054, Russia

Location

Seoul National University Bundang Hospital Gyeonggi-do

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Dong-A University Hospital

Busan, 602715, South Korea

Location

Korea University Anam Hospital

Seoul, 02481, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Reina Sofia

Córdoba, Córdoba, 14004, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HM Madrid Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Changhua Christian Medical Foundation Changhua Christian Hospital

Changhua, 500006, Taiwan

Location

Chang Gung Memorial Hospital, Chiayi

Chiayi City, 613, Taiwan

Location

E-DA Cancer Hospital

Kaohsiung City, 82445, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan District, 333, Taiwan

Location

Baskent University Adana Application and Research Center

Adana, 01229, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital

Ankara, 06105, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, 34098, Turkey (Türkiye)

Location

Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital

Istanbul, 34147, Turkey (Türkiye)

Location

Inonu Uni. Med. Fac.

Malatya, 44280, Turkey (Türkiye)

Location

CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU

Dnipro, 49102, Ukraine

Location

Communal Non-profit Enterprise Regional Center of Oncology

Kharkiv, 61070, Ukraine

Location

CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection

Kharkiv, 61166, Ukraine

Location

Medical Center of Limited Liability Company Medical Center Concilium Medical

Kyiv, 04050, Ukraine

Location

Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council

Lutsk, 43018, Ukraine

Location

Communal Institution Odesa Regional Clinical Hospital

Odesa, 65025, Ukraine

Location

CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology

Sumy, 40022, Ukraine

Location

Zaporizhzhya City Clinical Hospital #3

Zaporizhzhia, 69032, Ukraine

Location

Related Publications (2)

  • Qin S, Gu S, Chan SL, Bai Y, Ren Z, Lin X, Chen Z, Jia W, Jin Y, Guo Y, Hu X, Meng Z, Liang J, Xiong J, Ren H, Yang F, Li W, Chen Y, Zeng Y, Xu L, Yuan X, Li D, Sultanbaev A, Pazgan-Simon M, Pisetska M, Melisi D, Ponomarenko D, Du J, Shi W, Cheng AL, Kaseb A, Vogel A; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): final analysis of a randomised, open-label, international, phase 3 study. Lancet Oncol. 2025 Dec;26(12):1598-1611. doi: 10.1016/S1470-2045(25)00543-1.

  • Qin S, Chan SL, Gu S, Bai Y, Ren Z, Lin X, Chen Z, Jia W, Jin Y, Guo Y, Hu X, Meng Z, Liang J, Cheng Y, Xiong J, Ren H, Yang F, Li W, Chen Y, Zeng Y, Sultanbaev A, Pazgan-Simon M, Pisetska M, Melisi D, Ponomarenko D, Osypchuk Y, Sinielnikov I, Yang TS, Liang X, Chen C, Wang L, Cheng AL, Kaseb A, Vogel A; CARES-310 Study Group. Camrelizumab plus rivoceranib versus sorafenib as first-line therapy for unresectable hepatocellular carcinoma (CARES-310): a randomised, open-label, international phase 3 study. Lancet. 2023 Sep 30;402(10408):1133-1146. doi: 10.1016/S0140-6736(23)00961-3. Epub 2023 Jul 24.

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

camrelizumabapatinibSorafenib

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Results Point of Contact

Title
Yongli Xie
Organization
Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Study Officials

  • Shukui Qin, MD

    Eastern Theater General Hospital,QinHuai District Medical Area

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 28, 2018

First Posted

December 5, 2018

Study Start

June 10, 2019

Primary Completion

February 8, 2022

Study Completion

June 14, 2023

Last Updated

February 6, 2024

Results First Posted

February 6, 2024

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will not share

Locations