Clinical trial NCT03764293: A Study to Evaluate SHR-1210 in Combination With Apatinib as First-Line Therapy in Patients With Advanced HCC
Official title: A Randomized, Open-Label, International, Multi-Center, Phase 3 Clinical Study of PD-1 Antibody SHR-1210 Plus Apatinib Mesylate Versus Sorafenib as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Previously Received Systemic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Locally Advanced or Metastatic and Unresectable HCC
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-12-05
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Progression-free Survival (PFS) Evaluated by the Blinded Independent Review Committee (BIRC) Based on RECIST v1.1
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)-Moores Cancer Center
state: California
city: Orange
country: United States
facility: University of California - Irvine
state: California
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: New York
country: United States
facility: Cornell University Weill Cornell Medical College
state: New York
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires de Bruxelles Hopital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: UZA
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Hefei
country: China
facility: Anhui Provincal Cancer Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Provincal Hospital
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital Of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital Of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University International Hospital
state: Beijing
city: Chongqing
country: China
facility: The Second Hospital Affiliated To AMU
state: Chongqing
city: Chongqing
country: China
facility: The First Hospital Affiliated To AMU
state: Chongqing
city: Chongqing
country: China
facility: TheThird Affiliated Hospital ,Army Medical University
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of ChongQing Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Lanzhou
country: China
facility: The 940th Hospital of the joint logistic support force of People's Liberation Army
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: NanFang Hospital of Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The first affiliated hospital of guangxi medical university
state: Guangxi
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Eastern Theater General Hospital, Qinhuai District Medical Area
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital Of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shengyang
country: China
facility: The Sixth People's Hospital of Shengyang
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital Affiliated to Shandong University
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Si Chuan
city: Chengdu
country: China
facility: Sichuan Cancer Hospital&Institute
state: Sichuan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: ZheJiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Ponticelli
country: Italy
facility: A.S.L. Napoli 1 Centro Ospedale del Mare
state: Napoli
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Cagliari
country: Italy
facility: Azienda Ospedaliero-Universitaria
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital Gyeonggi-do
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia
city: Gliwice
country: Poland
facility: Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Poznan
country: Poland
facility: Przychodnia Med-Polonia Sp. z o.o.
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Onkologii
city: Warszawa
country: Poland
facility: Centrum Zdrowia MDM
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Wroclaw
country: Poland
facility: NZOZ Centrum Badan Klinicznych
city: Arkhangelsk
country: Russian Federation
facility: SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
city: Chelyabinsk
country: Russian Federation
facility: SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
city: Irkutsk
country: Russian Federation
facility: Irkutsk Regional Oncology Dispensary
city: Krasnodar
country: Russian Federation
facility: SBIH " Clinical Oncological Dispensary # 1"
city: Kursk
country: Russian Federation
facility: RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee
city: Moscow
country: Russian Federation
facility: "VitaMed" LLC
city: Moscow
country: Russian Federation
facility: SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare departement
city: Novosibirsk
country: Russian Federation
facility: CJSC Avicenna
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBIH "City Clinical Oncological Dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
city: Ufa
country: Russian Federation
facility: SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Córdoba
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Changhua
country: Taiwan
facility: Changhua Christian Medical Foundation Changhua Christian Hospital
city: Chiayi City
country: Taiwan
facility: Chang Gung Memorial Hospital, Chiayi
city: Kaohsiung
country: Taiwan
facility: E-DA Cancer Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Adana
country: Turkey
facility: Baskent University Adana Application and Research Center
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital
city: Malatya
country: Turkey
facility: Inonu Uni. Med. Fac.
city: Dnipro
country: Ukraine
facility: CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU
city: Kharkiv
country: Ukraine
facility: Communal Non-profit Enterprise Regional Center of Oncology
city: Kharkiv
country: Ukraine
facility: CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
city: Kyiv
country: Ukraine
facility: Medical Center of Limited Liability Company Medical Center Concilium Medical
city: Lutsk
country: Ukraine
facility: Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council
city: Odesa
country: Ukraine
facility: Communal Institution Odesa Regional Clinical Hospital
city: Sumy
country: Ukraine
facility: CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology
city: Zaporizhzhia
country: Ukraine
facility: Zaporizhzhya City Clinical Hospital #3
Study officials:
affiliation: Eastern Theater General Hospital,QinHuai District Medical Area
name: Shukui Qin, MD
role: PRINCIPAL_INVESTIGATOR
References: