A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC
- Conditions
- Locally Advanced or Metastatic and Unresectable HCC
- Interventions
- Registration Number
- NCT03764293
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 543
- 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
- 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
- Active known, or suspected autoimmune disease
- Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first administration of study treatment
- Use of potent CYP3A4 inducers or inhibitors within 2 weeks prior to the signature of ICF
- Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug
- Severe infection within 4 weeks prior to the start of study treatment
- Palliative radiotherapy for non-target lesions to control symptoms is allowed, but it must be completed at least 2 weeks prior to the start of study treatment
- Treatment of other investigational product(s) within 28 days prior to the start of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Sorafenib Sorafenib SHR-1210 SHR-1210 SHR-1210+Apatinib SHR-1210 Apatinib SHR-1210+Apatinib
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 3 years OS was defined as the time from randomization to death from any cause.
Progression-free Survival (PFS) Evaluated by the Blinded Independent Review Committee (BIRC) Based on RECIST v1.1 Up to approximately 3 years 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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to approximately 3 years ORR defined as the percentage of subjects with complete response (CR) or partial response (PR) evaluated by the BIRC or investigator based on RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Overall Response (OR)=CR+PR.
Duration of Response (DOR) Up to approximately 3 years DOR defined as time from the date of first record of objective response (CR or PR) to the first occurrence of radiological progression or death, whichever comes first, evaluated by the BIRC or investigator based on RECIST v1.1. Complete response (CR) was defined as Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.
Disease Control Rate (DCR) Up to approximately 3 years DCR defined as the percentage of subjects with complete response, partial response or stable disease (SD) ≥ 8 weeks evaluated by the BIRC or investigator based on RECIST v1.1. Complete response (CR) was defined as Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Trial Locations
- Locations (121)
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
The 940th Hospital of the joint logistic support force of People's Liberation Army
🇨🇳Lanzhou, Gansu, China
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
The first affiliated hospital of guangxi medical university
🇨🇳Nanning, Guangxi, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology
🇨🇳Wuhan, Hubei, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Eastern Theater General Hospital, Qinhuai District Medical Area
🇨🇳Nanjing, Jiangsu, China
AZ Maria Middelares
🇧🇪Gent, Belgium
West China Hospital of Sichuan University
🇨🇳Chengdu, Si Chuan, China
Cliniques Universitaires de Bruxelles Hopital Erasme
🇧🇪Bruxelles, Belgium
Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
🇵🇱Gliwice, Poland
Przychodnia Med-Polonia Sp. z o.o.
🇵🇱Poznan, Poland
University of Maryland
🇺🇸Baltimore, Maryland, United States
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
Azienda Ospedaliero-Universitaria
🇮🇹Cagliari, Italy
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
AZ Groeninge
🇧🇪Kortrijk, Belgium
Pamela Youde Nethersole Eastern Hospital
🇭🇰Hong Kong, Hong Kong
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Italy
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee
🇷🇺Kursk, Russian Federation
CJSC Avicenna
🇷🇺Novosibirsk, Russian Federation
BHI of Omsk region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
Pavlov First Saint Petersburg State Medical University
🇷🇺Saint-Petersburg, Russian Federation
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Inonu Uni. Med. Fac.
🇹🇷Malatya, Turkey
Communal Non-profit Enterprise Regional Center of Oncology
🇺🇦Kharkiv, Ukraine
Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council
🇺🇦Lutsk, Ukraine
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin
🇩🇪Berlin, Germany
"VitaMed" LLC
🇷🇺Moscow, Russian Federation
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
A.S.L. Napoli 1 Centro Ospedale del Mare
🇮🇹Ponticelli, Napoli, Italy
Pratia MCM Krakow
🇵🇱Krakow, Poland
SPb SBIH "City Clinical Oncological Dispensary"
🇷🇺Saint-Petersburg, Russian Federation
Baskent University Adana Application and Research Center
🇹🇷Adana, Turkey
Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital
🇹🇷Istanbul, Turkey
CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology
🇺🇦Sumy, Ukraine
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Ajou University Hospital
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
🇷🇺Chelyabinsk, Russian Federation
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
🇷🇺Saint-Petersburg, Russian Federation
SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
🇷🇺Ufa, Russian Federation
E-DA Cancer Hospital
🇨🇳Kaohsiung, Taiwan
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
🇹🇷Ankara, Turkey
CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
🇺🇦Dnipro, Ukraine
SBIH " Clinical Oncological Dispensary # 1"
🇷🇺Krasnodar, Russian Federation
Chang Gung Memorial Hospital, Chiayi
🇨🇳Chiayi City, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan, Taiwan
CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
🇺🇦Kharkiv, Ukraine
Communal Institution Odesa Regional Clinical Hospital
🇺🇦Odesa, Ukraine
SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare departement
🇷🇺Moscow, Russian Federation
University of California San Diego (UCSD)-Moores Cancer Center
🇺🇸La Jolla, California, United States
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology
🇨🇳Wuhan, Hubei, China
The First Hospital Affiliated To AMU
🇨🇳Chongqing, Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
The Fourth Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
UZA
🇧🇪Edegem, Belgium
Anhui Provincal Cancer Hospital
🇨🇳Hefei, Anhui, China
The Center for Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Anhui Provincal Hospital
🇨🇳Hefei, Anhui, China
The First Affiliated Hospital Of Anhui Medical University
🇨🇳Hefei, Anhui, China
The Second Affiliated Hospital Of Anhui Medical University
🇨🇳Hefei, Anhui, China
The Second Hospital Affiliated To AMU
🇨🇳Chongqing, Chongqing, China
Beijing cancer Hospital
🇨🇳Beijing, Beijing, China
Peking University International Hospital
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of ChongQing Medical University
🇨🇳Chongqing, Chongqing, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
🇮🇹Verona, Italy
Seoul National University Bundang Hospital Gyeonggi-do
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
🇮🇹Bologna, Italy
Centrum Zdrowia MDM
🇵🇱Warszawa, Poland
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
🇵🇱Warszawa, Poland
NZOZ Centrum Badan Klinicznych
🇵🇱Wroclaw, Poland
SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
🇷🇺Arkhangelsk, Russian Federation
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Irkutsk Regional Oncology Dispensary
🇷🇺Irkutsk, Russian Federation
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Changhua Christian Medical Foundation Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Ankara City Hospital
🇹🇷Ankara, Turkey
Zaporizhzhya City Clinical Hospital #3
🇺🇦Zaporizhzhia, Ukraine
Medical Center of Limited Liability Company Medical Center Concilium Medical
🇺🇦Kyiv, Ukraine
Hospital Universitario HM Madrid Sanchinarro
🇪🇸Madrid, Spain
University of California - Irvine
🇺🇸Orange, California, United States
Cornell University Weill Cornell Medical College
🇺🇸New York, New York, United States
Chinese Academy of Medical Sciences Cancer Hospital
🇨🇳Beijing, Beijing, China
TheThird Affiliated Hospital ,Army Medical University
🇨🇳Chongqing, Chongqing, China
Sun Yat-sen Memorial Hospital, Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
NanFang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Sixth People's Hospital of Shengyang
🇨🇳Shengyang, Liaoning, China
The First Affiliated Hospital Of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Shandong Cancer Hospital Affiliated to Shandong University
🇨🇳Jinan, Shandong, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
Zhongshan Hospital, Fudan University
🇨🇳Shanghai, Shanghai, China
Shanghai Changhai Hospital
🇨🇳Shanghai, Shanghai, China
Sichuan Cancer Hospital&Institute
🇨🇳Chengdu, Sichuan, China
Sir Run Run Shaw Hospital
🇨🇳Hangzhou, Zhejiang, China
ZheJiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
The Chinese University of Hong Kong
🇭🇰Shatin, Hong Kong
Tuen Mun Hospital
🇭🇰Hong Kong, Hong Kong
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Centrum Medyczne Pratia Gdynia
🇵🇱Gdynia, Poland
Wielkopolskie Centrum Onkologii
🇵🇱Poznan, Poland
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Córdoba, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
The University of Hong Kong
🇭🇰Hong Kong, Hong Kong