NIPH Clinical Trials Search

JRCT ID: jRCTs071200051

Registered date:13/11/2020

Combination Therapy with Atezolizumab plus Bevacizumab for TACE Unsuitable Patients in Intermediate Stage Up-to-Seven Out Hepatocellular Carcinoma - a phase II study-

Basic Information

Recruitment status Not Recruiting
Health condition(s) or Problem(s) studiedHepatocellular Carcinoma
Date of first enrollment09/12/2020
Target sample size70
Countries of recruitment
Study typeInterventional
Intervention(s)[Atezo+Bev therapy] In patients with unresectable intermediate stage up-to-seven out hepatocellular carcinoma, atezolizumab 1200 mg/body + bevacizumab 15 mg/kg will be infused once every 3 weeks.


Primary OutcomeProgression-free survival (PFS) (mRECIST; INV)
Secondary OutcomeObjective response rate (ORR) (mRECIST, RECIST ver. 1.1; INV) PFS (RECIST ver. 1.1; INV) Duration of response (DoR) Overall survival (OS) Safety (the nature and incidence by Grade of adverse events, changes over time in albumin-bilirubin [ALBI] / Modified ALBI [mALBI] score, changes over time in Child-Pugh score, etc.)

Key inclusion & exclusion criteria

Age minimum>= 20age old
Age maximumNot applicable
Include criteria(1)Personal written informed consent is obtained after the study has been fully explained. (2)Unresectable hepatocellular carcinoma (3)>= 20 years of age at enrollment (4)No vascular invasion / extrahepatic metastasis (5)Up-to-seven out population per Clinical Practice Manual for Hepatocellular Carcinoma, fourth edition (6)Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 (7)No previous drug therapy for hepatocellular carcinoma (sorafenib, lenvatinib or immunotherapy) (8)At least 1 intrahepatic target lesion according to mRECIST Patients are ineligible if tumor lesion assessment by 3-phase contrast CT or 3-phase contrast MRI cannot be performed due to reasons such as allergy to contrast medium. (9)No previous TACE (10)Child-Pugh class A within 14 days before enrollment (11)Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days before enrollment. If multiple test results are available during the concerned period, the results closest to enrollment will be used. Blood transfusion or hematopoietic factor administration within 30 days before the date of measurements is not permitted. i.Neutrophil count: >= 1,500/microL ii.Platelet count: >= 60,000/microL iii.Aspartate aminotransferase (AST): <= 5 times upper limit of normal (ULN) iv.Alanine aminotransferase (ALT): <= 5 times ULN v.Total bilirubin: <= 3.0 mg/dL vi.Serum albumin: >= 2.8 g/dL vii.Serum creatinine: <= 1.5 times ULN viii.Urine protein: <= 2+ If >= 3+, urine protein / creatinine ratio: < 2.0 in spot urine (in case of 24-hour urine collection, urine protein < 2.0 g / 24 hr)
Exclude criteria(1)Current or recent (within 10 days before enrollment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purposes. (2)Untreated or incompletely treated esophageal and/or varices with bleeding or high risk for bleeding; a previous bleeding event due to esophageal and/or varices within 180 days before enrollment. Patients must undergo an esophagogastroduodenoscopy (EGD), and varices of all sizes (small to large) must be assessed and prophylactically treated per study site standard of care before enrollment. Patients who have undergone an EGD within 180 days before enrollment and in whom the presence of varices has been denied do not need to undergo a repeat procedure. (3)Thrombosis or embolism within 180 days before enrollment (4)Major surgical procedure within 28 days before enrollment (open chest, laparoscopy, thoracoscopic surgery, laparoscopic surgery, etc.); open biopsy or suturing for major trauma; or planned major surgical procedure during the study (open chest, laparoscopy) (5)Treatment with systemic immunostimulatory agents (interferon, interleukin 2 [IL-2], etc.) within 180 days before enrollment (6)Treatment with systemic immunosuppressive agents (corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tumor necrosis factor [TNF]-alpha agents, etc.) within 14 days before enrollment, or anticipated need for systemic immunosuppressive agents during the study treatment, with the following exceptions: treatment with mineralocorticoids (fludrocortisone, etc.) or corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, etc. (7)History within 180 days before enrollment or complication of autoimmune inflammatory disease (8)History of active double cancer and malignancies (synchronous malignancies, and asynchronous malignancies separated by a 3-year disease-free interval) (9)Participation in a study of an unapproved drug or other interventional study (including follow-up period) (10)Significant cardiovascular disease (New York Heart Association [NYHA] Class II or greater cardiac disease, myocardial infarction), unstable arrhythmias, or unstable angina within 90 days before enrollment (11)Pregnant, breastfeeding, positive pregnancy test (all women who have experienced menstruation within the last year will be tested), or women and men who are unwilling to use contraception during the study (12)History of hepatic encephalopathy (13)Any of the following comorbidities: i. Uncontrolled hypertension with or without antihypertensive agents ii. Clinically uncontrolled pleural effusion, pericardial effusion, or ascites iii. Severe infection (e.g., hospitalization for complications of infection, bacteremia, or severe pneumonia) within 28 days before enrollment, except for HBV or HCV iv. Human immunodeficiency virus (HIV) infection v. hemodialysis by renal failure (14)History of severe allergic or anaphylactic reactions or anaphylactic reactions to chimeric or humanized antibodies, or fusion proteins (15)History of hypersensitivity to Chinese hamster ovary cell-derived products, or any component of atezolizumab or bevacizumab (16)Otherwise unsuitable for the study in the opinion of the attending physician

Related Information


Public contact
Name Kazuomi Ueshima
Address 377-2 Ohnohigashi,Osaka-Sayama City,Osaka Osaka Japan 589-8511
Telephone +81-72-366-0221
Affiliation Kindai University Hospital
Scientific contact
Name Masatoshi Kudo
Address 377-2 Ohnohigashi,Osaka-Sayama City,Osaka Osaka Japan 589-8511
Telephone +81-72-366-0221
Affiliation Kindai University Hospital