A Study of Atezolizumab in Combination With Bevacizumab Compared With Sorafenib in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT03434379
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy and safety of atezolizumab in combination with bevacizumab compared with sorafenib in participants with locally advanced or metastatic Hepatocellular Carcinoma (HCC) who have received no prior systemic treatment.
- Detailed Description
The participants will be randomized in a 2:1 ratio to one of the two treatment arms: Arm A (experimental arm): Atezolizumab +bevacizumab; Arm B (control arm): Sorafenib
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 558
- Locally advanced or metastatic and/or unresectable Hepatocellular Carcinoma (HCC)
- No prior systemic therapy for HCC. Previous use of herbal therapies/traditional Chinese medicines with anti-cancer activity included in the label is allowed, provided that these medications are discontinued prior to randomization.
- At least one measurable untreated lesion
- ECOG Performance Status of 0 or 1
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent
- For men: agreement to remain abstinent
- Child-Pugh class A
- History of leptomeningeal disease
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- Known active tuberculosis
- History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, or 1 month after the last dose of sorafenib
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
- A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
- Moderate or severe ascites
- History of hepatic encephalopathy
- Co-infection of HBV and HCV
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled or symptomatic hypercalcemia
- Treatment with systemic immunostimulatory agents
- Inadequately controlled arterial hypertension
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Evidence of bleeding diathesis or significant coagulopathy
- History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration
- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
- Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses
- Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure
- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab + Bevacizumab Atezolizumab Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator Atezolizumab + Bevacizumab Bevacizumab Participants will receive Atezolizumab + Bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator Sorafenib Sorafenib Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator
- Primary Outcome Measures
Name Time Method Progression Free Survival by Independent Review Facility-Assessment (PFS-IRF) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Overall Survival (OS) in the Global Population From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months) OS was defined as the time from randomization to death from any cause.
PFS-IRF Per RECIST v1.1 in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Overall Survival (OS) in the China Population From randomization to death from any cause up to the clinical cut off date (CCOD) of 29Aug2019 (up to approximately 18 months) and 31Aug2020 (up to approximately 30 months) OS was defined as the time from randomization to death from any cause.
- Secondary Outcome Measures
Name Time Method Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the Global Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. 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. OR=CR+PR
Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the Global Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to 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. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.
Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the Global Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver 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. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.
PFS-IRF Per HCC mRECIST in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the Global Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to 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. OR=CR+PR
Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the Global Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to 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. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.
PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
PFS-INV Per RECIST v1.1 by Baseline AFP in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed.
Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
PFS-IRF Per RECIST v1.1 by Baseline AFP in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm). Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed.
Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the China Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to 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. OR=CR+PR
TTP-IRF Per HCC mRECIST in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Objective Response Rate by IRF-Assessment (ORR-IRF) Per RECIST v1.1 in the Global Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) as determined by the IRF according to 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. OR=CR+PR
Maximum Serum Concentration (Cmax) of Atezolizumab at Cycle 1 in the Global Population Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) Objective Response Rate by IRF-Assessment (ORR-IRF) Per Hepatocellular Carcinoma (HCC) Modified RECIST (mRECIST) in the China Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ORR was defined as the percentage of participants with CR or PR as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver measuring only the residual vital tumor mass in the liver. 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. OR=CR+PR
Duration of Response by IRF-Assessment (DOR-IRF) Per RECIST v1.1 in the China Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to 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. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.
TTP-IRF Per HCC mRECIST in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Overall Survival by Baseline AFP in the Global Population From randomization to death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) OS was defined as the time from randomization to death from any cause. Subpopulations with baseline AFP \<400 ng/mL and AFP\>/= 400 ng/mL were analyzed.
Number of Participants With Adverse Events (AEs) in the Global Population Up to end of study (up to approximately 56 months) An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the Global Population Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 30 months) ORR by Investigator-Assessment (ORR-INV) Per RECIST v1.1 in the China Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) ORR was defined as the percentage of participants with CR or PR as determined by the investigator according to 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. OR=CR+PR
PFS-IRF Per HCC mRECIST in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Time to Deterioration (TTD) in the Global Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) TTD was defined as the time from randomization to the first deterioration (decrease from baseline of \>/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.
Trough Serum Concentration (Cmin) of Atezolizumab in the Global Population Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days) Duration of Response by Investigator Assessment (DOR-INV) Per RECIST v1.1 in the China Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the investigator according to 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. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.
PFS by Investigator Assessment (PFS-INV) Per RECIST v1.1 in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) PFS was defined as the time from randomization to the first occurrence of progressive disease or death from any cause whichever occurs first as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Duration of Response by IRF Assessment (DOR-IRF) Per HCC mRECIST in the China Population Randomization up to CCOD of 29Aug2019 (up to approximately 18 months) DOR was defined as the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression (PD) or death was documented, whichever occurs first as determined by the IRF according to HCC mRECIST. HCC mRECIST differentiates between vital tumor and necrotic areas in the liver, measuring only the residual vital tumor mass in the liver 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. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 mm.
Time to Progression (TTP) by IRF Assessment (TTP-IRF) Per RECIST v1.1 in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Time to Deterioration (TTD) in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) TTD was defined as the time from randomization to the first deterioration (decrease from baseline of \>/= 10 points) in the patient-reported health-related global health status/quality of life (GHS /HRQoL), physical function or role function scales of the European Organization for Research and Treatment of Cancer quality-of-life questionnaire for cancer (EORTC) QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab in the China Population Baseline and post-baseline on Day 1 (pre-dose) of Cycles 2, 3, 4, 8, 12, 16 (cycle length = 21 days) and treatment discontinuation visit (up to approximately 18 months) Maximum Serum Concentration (Cmax) of Atezolizumab in the China Population Post-dose on Day 1 of Cycle 1 (cycle length = 21 days) TTP by Investigator Assessment (TTP-INV) Per RECIST v1.1 in the China Population Randomization to the first occurrence of disease progression or death from any cause up to CCOD of 29Aug2019 (up to approximately 18 months) Time to progression was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Number of Participants With Adverse Events (AEs) in the China Population Up to end of study (up to approximately 56 months) An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Trough Serum Concentration (Cmin) of Atezolizumab in the China Population Pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length = 21 days)
Trial Locations
- Locations (119)
Hokkaido University Hospital
🇯🇵Hokkaido, Japan
Campus Virchow-Klinikum Charité Centrum 13; Medizinische Klinik; Abt.Hepatologie u.Gastroenterologie
🇩🇪Berlin, Germany
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Hopital Timone Adultes; Gastro Enterologie
🇫🇷Marseille, France
Hopital Hotel Dieu Et Hme; Hepatologie Gastro Enterologie
🇫🇷Nantes, France
Hopital Charles Nicolle; Gastroenterologie
🇫🇷Rouen, France
Dolno?l?skie Centrum Onkologii; Oddzia? Onkologii Klinicznej i Chemioterapii
🇵🇱Wroc?aw, Poland
Banner MD Anderson Cancer Center
🇺🇸Greeley, Colorado, United States
St. Josephs Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Kaiser Permanente - San Francisco Medical Center
🇺🇸San Francisco, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Sir Run Run Shaw Hospital
🇨🇳Hangzhou City, China
City of Hope
🇺🇸Duarte, California, United States
Uni of California - San Diego; Cancer Center & Dept of Medicine
🇺🇸La Jolla, California, United States
Kaiser Permanente Northern California
🇺🇸Novato, California, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸Sacramento, California, United States
University of California Los Angeles
🇺🇸Santa Monica, California, United States
Kaiser Permanente - Walnut Creek
🇺🇸Walnut Creek, California, United States
Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department
🇨🇳Hangzhou City, China
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of New Mexico Comprehensive Cancer Center
🇺🇸Albuquerque, New Mexico, United States
M.D Anderson Cancer Center; Uni of Texas At Houston
🇺🇸Houston, Texas, United States
Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
🇺🇸New York, New York, United States
Washington University; Wash Uni. Sch. Of Med
🇺🇸Saint Louis, Missouri, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
General Hospital of Jinan Military Command of PLA
🇨🇳Jinan, China
Swedish Cancer Inst.
🇺🇸Seattle, Washington, United States
Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
The Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
Centre hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre - Glen Site
🇨🇦Montreal, Quebec, Canada
Peking Union Medical College Hospital
🇨🇳Beijing City, China
the First Hospital of Jilin University
🇨🇳Changchun, China
The First People's Hospital of Foshan; Local Ethic Committee
🇨🇳Foshan, China
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou City, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Jilin Cancer Hospital
🇨🇳Changchun, China
Hunan Cancer Hospital
🇨🇳Changsha CITY, China
The 900th Hospital of PLA joint service support force
🇨🇳Fuzhou, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, China
The First Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Anhui Province Cancer Hospital
🇨🇳Hefei City, China
The 81st Hospital of P.L.A.
🇨🇳Nanjing City, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai City, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Tongji Hosp, Tongji Med. Col, Huazhong Univ. of Sci. & Tech
🇨🇳Wuhan, China
Masarykuv onkologicky ustav
🇨🇿Brno, Czechia
Fakultni nemocnice Olomouc; Onkologicka klinika
🇨🇿Olomouc, Czechia
Hopital Claude Huriez;Gastro Enterologie
🇫🇷Lille, France
Hopital De La Croix Rousse; Hepatologie Gastro Enterologie
🇫🇷Lyon, France
Hopital Saint-Eloi; Hepatologie-Gastro-Enterologie
🇫🇷Montpellier, France
CHU Nice - Hôpital de l'Archet 2; service Hepato gastro enterologie
🇫🇷Nice Cedex, France
Hopital Hautepierre; Gastro Enterologie
🇫🇷Strasbourg, France
Hôpital d'Adultes; Service hépato-gastro-entérologie
🇫🇷Vandoeuvre-les-nancy, France
Institut Gustave Roussy; Gastro-Enterologie
🇫🇷Villejuif, France
Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I
🇩🇪Frankfurt, Germany
Universitaetsklinikum Hamburg-Eppendorf; I. Medizinische Klinik - Gastroenterologie
🇩🇪Hamburg, Germany
Med. Hochschule Hannover; Gastroenterologie
🇩🇪Hannover, Germany
Universitätsklinikum Leipzig Medizinische Klinik II Gastroenterolog. u. Hepatolog.
🇩🇪Leipzig, Germany
Uniklinik Mainz; I. Medizinische Klinik
🇩🇪Mainz, Germany
Klinikum der Uni Regensburg; Klinik f.Innere Medizin I Abt. Hämatologie und Internistische Onkologie
🇩🇪Regensburg, Germany
Queen Mary Hospital; Dept. Of Haematology & Oncology
🇭🇰Hong Kong, Hong Kong
Az. Osp. Rummo; Oncologia Medica
🇮🇹Benevento, Campania, Italy
Prince of Wales Hosp; Dept. Of Clinical Onc
🇭🇰Shatin, Hong Kong
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
🇮🇹Meldola, Emilia-Romagna, Italy
Az. Osp. S. Luigi Gonzaga; Divisione Di Oncologia Medica
🇮🇹Orbassano, Piemonte, Italy
A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia
🇮🇹Cagliari, Sardegna, Italy
Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico
🇮🇹Pisa, Toscana, Italy
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
🇮🇹Padova, Veneto, Italy
Chiba University Hospital
🇯🇵Chiba, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Kurume University Hospital
🇯🇵Fukuoka, Japan
Sapporo Kosei Genaral Hospital
🇯🇵Hokkaido, Japan
Kanazawa University Hospital
🇯🇵Ishikawa, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Saga-ken Medical Centre Koseikan
🇯🇵Saga, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
Japanese Red Cross Musashino Hospital
🇯🇵Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Jeollanam-do, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Tan Tock Seng Hospital; Oncology
🇸🇬Singapore, Singapore
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Ulsan University Hosiptal
🇰🇷Ulsan, Korea, Republic of
ID Clinic
🇵🇱Myslowice, Poland
SP ZOZ MSWiA z WARMINSKO-MAZURSKIM CENTRUM ONKOLOGII; CLINICAL ONCOLOGY, CLINICAL IMMUNOLOGY
🇵🇱Olsztyn, Poland
Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
🇵🇱Gdansk, Poland
FSBI "National Medical Research Center of Oncology N.N. Blokhin?; Clinical Biotechnologies
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Hospital Universitari Vall d'Hebron; Oncology
🇪🇸Barcelona, Spain
GBUZ Saint Petersburg Clinical Research Center of Specialized Types of Care (Oncology)
🇷🇺Saint Petersburg, Sankt Petersburg, Russian Federation
National Cancer Centre
🇸🇬Singapore, Singapore
Hospital Clinico San Carlos; Servicio de Oncologia
🇪🇸Madrid, Spain
National Cheng Kung University Hospital; Oncology
🇨🇳Tainan, Taiwan
Hospital Universitario Miguel Servet; Servicio de Oncologia Medica
🇪🇸Zaragoza, Spain
Centro Integral Oncologico Clara Campal; Servicio de Oncología
🇪🇸Madrid, Spain
Chang Gung Memorial Hospital-Linkou; Dept of Oncology
🇨🇳Taoyuan County, Taiwan
Veterans General Hospital; Cancer Center
🇨🇳Taipei, Taiwan
National Taiwan Uni Hospital; Dept of Oncology
🇨🇳Taipei, Taiwan
Chi-Mei Medical Centre; Hematology & Oncology
🇨🇳Tainan, Taiwan
King'S College Hospital
🇬🇧London, United Kingdom
Royal Free Hospital; Dept of Oncology
🇬🇧London, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸Madrid, Spain
Georgetown University
🇺🇸Washington, District of Columbia, United States
Bankstown-Lidcombe Hospital
🇦🇺Bankstown, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Beijing Friendship Hospital
🇨🇳Beijing, China
Christie Hospital Nhs Trust; Medical Oncology
🇬🇧Manchester, United Kingdom
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States