Locally Advanced or Metastatic and Unresectable HCC Clinical Trial
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
| Verified date | February 2023 |
| Source | Jiangsu HengRui Medicine Co., Ltd. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 543 |
| Est. completion date | June 14, 2023 |
| Est. primary completion date | February 8, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Cliniques Universitaires de Bruxelles Hopital Erasme | Bruxelles | |
| Belgium | Cliniques Universitaires Saint-Luc | Bruxelles | |
| Belgium | UZA | Edegem | |
| Belgium | AZ Maria Middelares | Gent | |
| Belgium | AZ Groeninge | Kortrijk | |
| China | Beijing cancer Hospital | Beijing | Beijing |
| China | Chinese Academy of Medical Sciences Cancer Hospital | Beijing | Beijing |
| China | Peking University International Hospital | Beijing | Beijing |
| China | Jilin Cancer Hospital | Changchun | Jilin |
| China | The First Hospital of Jilin University | Changchun | Jilin |
| China | Hunan Cancer Hospital | Changsha | Hunan |
| China | Sichuan Cancer Hospital&Institute | Chengdu | Sichuan |
| China | West China Hospital of Sichuan University | Chengdu | Si Chuan |
| China | The First Hospital Affiliated To AMU | Chongqing | Chongqing |
| China | The Second Affiliated Hospital of ChongQing Medical University | Chongqing | Chongqing |
| China | The Second Hospital Affiliated To AMU | Chongqing | Chongqing |
| China | TheThird Affiliated Hospital ,Army Medical University | Chongqing | Chongqing |
| China | Fujian Medical University Union Hospital | Fuzhou | Fujian |
| China | NanFang Hospital of Southern Medical University | Guangzhou | Guangdong |
| China | Sun Yat-sen Memorial Hospital, Sun Yat-Sen University | Guangzhou | Guangdong |
| China | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong |
| China | Sir Run Run Shaw Hospital | Hangzhou | Zhejiang |
| China | The First Affiliated Hospital, Zhejiang University | Hangzhou | Zhejiang |
| China | ZheJiang Cancer Hospital | Hangzhou | Zhejiang |
| China | Harbin Medical University Cancer Hospital | Harbin | Heilongjiang |
| China | Anhui Provincal Cancer Hospital | Hefei | Anhui |
| China | 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 | Shandong Cancer Hospital Affiliated to Shandong University | Jinan | Shandong |
| China | The 940th Hospital of the joint logistic support force of People's Liberation Army | Lanzhou | Gansu |
| China | The First Affiliated Hospital Of Nanchang University | Nanchang | Jiangxi |
| China | Eastern Theater General Hospital, Qinhuai District Medical Area | Nanjing | Jiangsu |
| China | The first affiliated hospital of guangxi medical university | Nanning | Guangxi |
| China | Fudan University Shanghai Cancer Center | Shanghai | Shanghai |
| China | Shanghai Changhai Hospital | Shanghai | Shanghai |
| China | Zhongshan Hospital, Fudan University | Shanghai | Shanghai |
| China | The Sixth People's Hospital of Shengyang | Shengyang | Liaoning |
| China | Liaoning Cancer Hospital | Shenyang | Liaoning |
| China | The Fourth Hospital of Hebei Medical University | Shijiazhuang | Hebei |
| China | Tongji hospital,Tongji Medical College,Huazhong University of Science&Technology | Wuhan | Hubei |
| China | Wuhan Union Hospital,Tongji Medical College,Huazhong University of Science&Technology | Wuhan | Hubei |
| Germany | Charite Universitaetsmedizin Berlin - Campus Virchow-Klinikum Berlin | Berlin | |
| Hong Kong | Pamela Youde Nethersole Eastern Hospital | Hong Kong | |
| Hong Kong | The University of Hong Kong | Hong Kong | |
| Hong Kong | Tuen Mun Hospital | Hong Kong | |
| Hong Kong | The Chinese University of Hong Kong | Shatin | |
| Italy | Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS | Bologna | |
| Italy | Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) | Brescia | |
| Italy | Azienda Ospedaliero-Universitaria | Cagliari | |
| Italy | Azienda Ospedaliera Universitaria Careggi | Firenze | |
| Italy | Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico | Milano | |
| Italy | A.S.L. Napoli 1 Centro Ospedale del Mare | Ponticelli | Napoli |
| Italy | Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Roma | |
| Italy | Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) | Verona | |
| Korea, Republic of | Dong-A University Hospital | Busan | |
| Korea, Republic of | Seoul National University Bundang Hospital Gyeonggi-do | Seongnam-si | Gyeonggi-do |
| Korea, Republic of | Asan Medical Center | Seoul | |
| Korea, Republic of | Korea University Anam Hospital | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | |
| Korea, Republic of | Ajou University Hospital | Suwon | Gyeonggi-do |
| Korea, Republic of | The Catholic University of Korea, St. Vincent's Hospital | Suwon-si | Gyeonggi-do |
| Poland | Centrum Medyczne Pratia Gdynia | Gdynia | |
| Poland | Centrum Onkologii-Instytut im.M.Sklodowskiej Curie | Gliwice | |
| Poland | Pratia MCM Krakow | Krakow | |
| Poland | Przychodnia Med-Polonia Sp. z o.o. | Poznan | |
| Poland | Wielkopolskie Centrum Onkologii | Poznan | |
| Poland | Centrum Zdrowia MDM | Warszawa | |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy | Warszawa | |
| Poland | NZOZ Centrum Badan Klinicznych | Wroclaw | |
| Russian Federation | SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary" | Arkhangelsk | |
| Russian Federation | SBHI Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine | Chelyabinsk | |
| Russian Federation | Irkutsk Regional Oncology Dispensary | Irkutsk | |
| Russian Federation | SBIH " Clinical Oncological Dispensary # 1" | Krasnodar | |
| Russian Federation | RBIH "Kursk regional clinical oncology dispensary" of Kursk Region Healthcare Committee | Kursk | |
| Russian Federation | "VitaMed" LLC | Moscow | |
| Russian Federation | SBIH of Moscow city "Moscow city oncology hospital ?62" of Moscow Healthcare departement | Moscow | |
| Russian Federation | CJSC Avicenna | Novosibirsk | |
| Russian Federation | BHI of Omsk region "Clinical Oncology Dispensary" | Omsk | |
| Russian Federation | FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov" | Saint-Petersburg | |
| Russian Federation | Pavlov First Saint Petersburg State Medical University | Saint-Petersburg | |
| Russian Federation | SPb SBIH "City Clinical Oncological Dispensary" | Saint-Petersburg | |
| Russian Federation | SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan | Ufa | |
| Spain | Hospital Universitario Reina Sofia | Cordoba | Córdoba |
| Spain | Hospital Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Universitario Clinico San Carlos | Madrid | |
| Spain | Hospital Universitario HM Madrid Sanchinarro | Madrid | |
| Spain | Hospital Universitario La Paz | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal | Madrid | |
| Spain | Hospital Universitari i Politecnic La Fe | Valencia | |
| Taiwan | Changhua Christian Medical Foundation Changhua Christian Hospital | Changhua | |
| Taiwan | Chang Gung Memorial Hospital, Chiayi | Chiayi City | |
| Taiwan | E-DA Cancer Hospital | Kaohsiung | |
| Taiwan | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung | |
| Taiwan | National Cheng Kung University Hospital | Tainan | |
| Taiwan | National Taiwan University Hospital | Taipei | |
| Taiwan | Taipei Veterans General Hospital | Taipei | |
| Taiwan | Chang Gung Memorial Hospital, Linkou | Taoyuan | |
| Turkey | Baskent University Adana Application and Research Center | Adana | |
| Turkey | Ankara City Hospital | Ankara | |
| Turkey | Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital | Ankara | |
| Turkey | Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital | Istanbul | |
| Turkey | Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty | Istanbul | |
| Turkey | Inonu Uni. Med. Fac. | Malatya | |
| Ukraine | CNE"City Clin Hosp#4"of Dnipro City Council Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU | Dnipro | |
| Ukraine | CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection | Kharkiv | |
| Ukraine | Communal Non-profit Enterprise Regional Center of Oncology | Kharkiv | |
| Ukraine | Medical Center of Limited Liability Company Medical Center Concilium Medical | Kyiv | |
| Ukraine | Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council | Lutsk | |
| Ukraine | Communal Institution Odesa Regional Clinical Hospital | Odesa | |
| Ukraine | CNCE of SRC Sumy Reg Clinical Oncology Dispensary, SSU, Chair of Oncology and Radiology | Sumy | |
| Ukraine | Zaporizhzhya City Clinical Hospital #3 | Zaporizhzhia | |
| United States | University of Maryland | Baltimore | Maryland |
| United States | Beverly Hills Cancer Center | Beverly Hills | California |
| United States | The Center for Cancer and Blood Disorders | Fort Worth | Texas |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | University of California San Diego (UCSD)-Moores Cancer Center | La Jolla | California |
| United States | Cornell University Weill Cornell Medical College | New York | New York |
| United States | University of California - Irvine | Orange | California |
| United States | Renovatio Clinical | The Woodlands | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Jiangsu HengRui Medicine Co., Ltd. |
United States, Belgium, China, Germany, Hong Kong, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Survival (OS) | OS was defined as the time from randomization to death from any cause. | Up to approximately 3 years | |
| Primary | 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 | Objective Response Rate (ORR) | 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. | Up to approximately 3 years | |
| Secondary | Disease Control Rate (DCR) | 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. | Up to approximately 3 years | |
| Secondary | Duration of Response (DOR) | 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. | Up to approximately 3 years |