A Study of Atezolizumab Plus Bevacizumab Versus Active Surveillance as Adjuvant Therapy in Patients With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection or Ablation
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT04102098
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy and safety of adjuvant therapy with atezolizumab plus bevacizumab compared with active surveillance in participants with completely resected or ablated hepatocellular carcinoma (HCC) who are at high risk for disease recurrence.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 668
- Participants with a first diagnosis of HCC who have undergone either a curative resection or ablation (radiofrequency ablation [RFA] or microwave ablation [MVA] only) within 4-12 weeks prior to randomization
- Documented diagnosis of HCC that has been completely resected or ablated (RFA or MVA only)
- Absence of major macrovascular invasion (except Vp1/Vp2) and extrahepatic spread
- Absence of extrahepatic spread as confirmed by CT or MRI scan of the chest, abdomen, pelvis, and head prior to and following curative procedure
- Full recovery from surgical resection or ablation within 4 weeks prior to randomization
- High risk for HCC recurrence after resection or ablation
- For patients who received post-operative transarterial chemoembolization: full recovery from the procedure within 4 weeks prior to randomization
- For patients with resected HCC, availability of a representative baseline tumor tissue sample
- ECOG Performance Status of 0 or 1
- Child-Pugh Class A status
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Evidence of residual, recurrent, or metastatic disease at randomization
- Clinically significant ascites
- History of hepatic encephalopathy
- Prior bleeding event due to untreated or incompletely treated esophageal and/or gastric varices within 6 months prior to randomization
- Have received more than 1 cycle of adjuvant TACE following surgical resection
- 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 CT scan
- Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1, unstable arrhythmia, or unstable angina
- 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
- Active tuberculosis
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of atezolizumab or within 6 months after the final dose of bevacizumab. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to Day 1 of Cycle 1.
- Co-infection with HBV and HCV
- Co-infection with HBV and hepatitis D viral infection
- Clinical significant uncontrolled or symptomatic hypercalcemia
- Any treatment for HCC prior to resection or ablation, including systemic therapy and locoregional therapy such as TACE
- Treatment with systemic immunostimulatory or immunosuppressive agents
- Inadequately controlled arterial hypertension
- History of hypertensive crisis or hypertensive encephalopathy
- Significant vascular disease
- Evidence of bleeding diathesis or significant coagulopathy
- Current or recent use of aspirin or full-dose oral or parenteral anticoagulants
- Core biopsy within 3 days of Day 1 of Cycle 1
- History of GI fistula, GI perforation, or intra-abdominal abscess
- Serious non-healing or dehiscing wound
- Major surgical procedure within four weeks
- Chronic daily treatment with a non-steroidal anti-inflammatory drug
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (atezolizumab plus bevacizumab) Bevacizumab Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity. Arm A (atezolizumab plus bevacizumab) Atezolizumab Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Recurrence-Free Survival (RFS), as Determined by IRF Baseline up to approximately 33 months RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an IRF, or death from any cause (whichever occurs first).
- Secondary Outcome Measures
Name Time Method RFS as Determined by the Investigator Baseline up to approximately 91 months RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an investigator, or death from any cause (whichever occurs first).
RFS Rate at 24 and 36 Months, as Assessed by the IRF Randomization up to 24 months and up to 36 months OS Rate at 24 and 36 Months Baseline to 24 and 36 months OS rate defined as the proportion of patients who have not experienced death from any cause at 24 and 36 months after randomization.
Overall Survival (OS) Baseline up to approximately 91 months OS is defined as the time from randomization to death from any cause.
RFS Rate at 24 and 36 Months, as Assessed by the Investigator Randomization up to 24 months and up to 36 months RFS in Pd-L1-High Subgroup Baseline up to approximately 91 months RFS after randomization as determined by the investigator and by an IRF, among patients in the PD-L1-high subgroup.
Percentage of Participants With Adverse Events Baseline up to approximately 91 months Time to Recurrence (TTR) Baseline up to approximately 91 months TTR defined as the time from randomization to first documented occurrence of intrahepatic or extrahepatic HCC, as determined by the investigator and by an IRF.
Time to Extrahepatic Spread (EHS) or Macrovascular Invasion Baseline up to approximately 91 months Time to EHS or macrovascular invasion after randomization, defined as the time from randomization to the first appearance of EHS or macrovascular invasion, as determined by the investigator.
Serum Concentration of Atezolizumab Prior to any drug administration on Day 1 of Cycles 1, 2, 3, 4, 8, 12, and 16, and 30 minutes after end of atezolizumab infusion on Day 1 of Cycle 1 (each cycle is 21 days) Serum concentration of atezolizumab.
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab Prior to any drug administration up to approximately 33 month Number of participants with anti-drug antibodies to atezolizumab.
Trial Locations
- Locations (134)
Tan Tock Seng Hospital
🇸🇬Singapore, Singapore
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Swedish Cancer Inst.
🇺🇸Seattle, Washington, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Lkh-Univ. Klinikum Graz
🇦🇹Graz, Austria
Klinikum Klagenfurt am Wörtersee
🇦🇹Klagenfurt, Austria
Medizinische Universität Wien
🇦🇹Wien, Austria
Imeldaziekenhuis
🇧🇪Bonheiden, Belgium
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
Hospital Sao Rafael - HSR
🇧🇷Salvador, Bahia, Brazil
Sociedade beneficente de senhoras Hospital Sirio Libanes
🇧🇷Brasilia, Distrito Federal, Brazil
Hospital do Cancer UOPECCAN
🇧🇷Cascavel, Paraná, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, São Paulo, Brazil
Gordon & Leslie Diamond Health Care Centre
🇨🇦Vancouver, British Columbia, Canada
McGill University Health Centre - Glen Site
🇨🇦Montreal, Quebec, Canada
Anhui Provincial Hospital
🇨🇳Anhui, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, China
Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, China
The First Hospital of Jilin University
🇨🇳Changchun City, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Daping Hospital of Third Military Medical University
🇨🇳Chongqing, China
The Second Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, China
Mengchao Hepatobiliary Hospital Of Fujian Medical University
🇨🇳Fuzhou City, China
Fujian Cancer Hospital
🇨🇳Fuzhou, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, China
Sun Yet-sen University Cancer Center
🇨🇳Guangzhou, China
Zhujiang Hospital, Southern Medical University
🇨🇳Guangzhou, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou City, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
Anhui Province Cancer Hospital
🇨🇳Hefei, China
The Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Shandong Cancer Hospital
🇨🇳Jinan, China
The 81st Hospital of P.L.A.
🇨🇳Nanjing City, China
Zhongda Hospital Affiliated to Southeast University
🇨🇳Nanjing, China
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, China
Guangxi Cancer Hospital of Guangxi Medical University
🇨🇳Nanning, China
The First Affiliate Hospital of Guangxi Medical University
🇨🇳Nanning, China
Huashan Hospital Affiliated to Fudan University
🇨🇳Shanghai City, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Zhongshan Hospital Fudan Unvierstiy
🇨🇳Shanghai, China
Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
The First Affiliated Hospital of China Medical University
🇨🇳Shenyang City, China
Shengjing Hospital of China Medical University
🇨🇳ShenYang, China
Tianjin Cancer Hospital
🇨🇳Tianjin, China
The Tumor Hospital of Xinjiang Medical University
🇨🇳Urumqi, China
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Renmin Hospital of Wuhan University
🇨🇳Wuhan, China
Hopital Jean Minoz
🇫🇷Besancon, France
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, China
Northern Jangsu People's Hospital
🇨🇳Yangzhou, China
Clinica CIMCA
🇨🇷San José, Costa Rica
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni Thomayerova Nemocnice
🇨🇿Praha, Czechia
Hôpital Avicenne - Groupement Hospitalier Universitaire Paris Seine St Denis
🇫🇷Bobigny Cedex, France
Hôpital Albert Michallon
🇫🇷La Tronche, France
Fondation Hopital Saint Joseph
🇫🇷Marseille, France
CHU Bordeaux - Hôpital Haut-Lévêque
🇫🇷Pessac, France
Hopital Robert Debre
🇫🇷Reims, France
Hopital de Pontchaillou
🇫🇷Rennes, France
CHU de Toulouse - Hôpital Rangueil
🇫🇷Toulouse Cedex 09, France
Hopitaux de Brabois - Gastro-Entereologie
🇫🇷Vandoeuvre-les-nancy, France
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik I.
🇩🇪Bonn, Germany
Klinik Johann Wolfgang von Goethe Uni
🇩🇪Frankfurt Am Main, Germany
Klinikum der Uni Regensburg
🇩🇪Regensburg, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong
Ospedale Regionale Di Parma
🇮🇹Parma, Emilia-Romagna, Italy
Ospedale Maggiore Policlinico
🇮🇹Milano, Lombardia, Italy
Chiba University Hospital
🇯🇵Chiba, Japan
Asst Santi Paolo E Carlo
🇮🇹Milano, Lombardia, Italy
Azlenda Ospendaliero-Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Ehime Prefectural Central Hospital
🇯🇵Ehime, Japan
Hiroshima University Hospital
🇯🇵Hiroshima, Japan
Sapporo Kosei General Hospital
🇯🇵Hokkaido, Japan
Hyogo Medical University Hospital
🇯🇵Hyogo, Japan
Japanese Red Cross Society Himeji Hospital
🇯🇵Hyogo, Japan
Kanazawa University Hospital
🇯🇵Ishikawa, Japan
Yokohama City University Medical Center
🇯🇵Kanagawa, Japan
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Osaka Red Cross Hospital
🇯🇵Osaka, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Tokushima University Hospital
🇯🇵Tokushima, Japan
Toranomon Hospital
🇯🇵Tokyo, Japan
Clinical hospital #1, FBHI Volga district medical center, Federal Medical and Biological Agency
🇷🇺Nizhny Novgorod, Niznij Novgorod, Russian Federation
Russian Scientific Center of Radiology and Surgical Technologies
🇷🇺Pesochny, Sankt Petersburg, Russian Federation
The University of Tokyo Hospital
🇯🇵Tokyo, Japan
Japanese Red Cross Musashino Hospital
🇯🇵Tokyo, Japan
National Cancer Centre
🇸🇬Singapore, Singapore
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Hospital Universitario Infanta Cristina
🇪🇸Badajoz, Spain
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
CHA Bundang Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Changhua Christian Hospital
🇨🇳Chang Hua, Taiwan
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Ajou University Medical Center
🇰🇷Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Ulsan University Hosiptal
🇰🇷Ulsan, Korea, Republic of
Filios Alta Medicina
🇲🇽Monterrey, Nuevo LEON, Mexico
Oaxaca Site Management Organization
🇲🇽Oaxaca, Mexico
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
Clínica San Gabriel
🇵🇪Lima, Peru
Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
🇵🇱Warszawa, Poland
First Moscow State Medical University n.a. I.M. Sechenov
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
Kaiser Permanente Los Angeles
🇺🇸Los Angeles, California, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Group of companies "Medci"
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
National Taiwan Uni Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation - Linkou
🇨🇳Taoyuan, Taiwan
Rajavithi Hospital
🇹🇭Bangkok, Thailand
Siriraj Hospital
🇹🇭Bangkok, Thailand
Chiang Rai Prachanukroh Hospital
🇹🇭Chiang Rai, Thailand
Chulabhorn Hospital
🇹🇭Lak Si, Thailand
Adana Baskent University Hospital
🇹🇷Adana, Turkey