A Study of TACE Combined With Atezolizumab Plus Bevacizumab or TACE Alone in Patients With Untreated Heaptocellular Carcionma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase III, Open-Label, Randomized Study of On-Demand TACE Combined With Atezolizumab Plus Bevacizumab (Atezo/Bev) or On-Demand TACE Alone in Patients With Untreated Heaptocellular Carcionma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04712643
• Other study ID #: ML42612
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 12, 2021
• Est. completion date: February 28, 2029

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of atezolizumab plus bevacizumab combined with on-demand TACE compared to on-demand TACE alone in participants with hepatocellular carcinoma who are at high risk of poorer outcome following TACE treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 342
• Est. completion date: February 28, 2029
• Est. primary completion date: February 28, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of HCC by histology/ cytology or clinical criteria

• Eligible for TACE treatment

• No prior systemic therapy for HCC, especially immunotherapy

• No prior locoregional therapy to the target lesion(s)

• At least one measurable untreated lesion

• ECOG Performance Status of 0-1

• Child-Pugh class A

Exclusion Criteria:

• Evidence of Vp3/4 and hepatic vein tumor thrombus (HVTT)

• Evidence of extrahepatic spread (EHS)

• Being a candidate for curative treatments

• Any condition representing a contraindication to TACE as determined by the investigators

• Active or history of autoimmune disease or immune deficiency

• 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

• Evidence of bleeding diathesis or significant coagulopathy

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle until participant experience loss of clinical benefit as evaluated by the investigator or unacceptable toxicity or withdrawal of informed consent.
• Becavizumab
Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle.

Device:
• Transarterial chemoembolization (TACE)
TACE will be performed by clinical demand.

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing City
China	Beijing You An Hospital; Digestive Dept	Beijing City
China	Peking University First Hospital	Beijing City
China	Hunan Cancer Hospital	Changsha CITY
China	Sichuan Cancer Hospital	Chengdu City
China	West China Hospital, Sichuan University; Surgical Oncology	Chengdu City
China	Southwest Hospital , Third Military Medical University	Chongqing
China	The First Affiliated Hospital, Chongqing Medical University	Chongqing
China	Fujian Cancer Hospital	Fuzhou
China	The 900th Hospital of PLA joint service support force	Fuzhou
China	Mengchao Hepatobiliary Hospital Of Fujian Medical University	Fuzhou City
China	The First Affiliated Hospital Of Fujian Medical University	Fuzhou City
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou City
China	Harbin Medical University Cancer Hospital; internal medicine	Harbin City
China	Anhui Provincial Hospital	Hefei
China	Jiangsu Cancer Hospital	Nanjing City
China	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City
China	The First Affiliate Hospital of Guangxi Medical University	Nanning
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning City
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Renji Hospital Shanghai Jiaotong University School of Medicine	Shanghai City
China	Zhongshan Hospital Fudan Unvierstiy	Shanghai City
China	Shengjing Hospital of China Medical University	ShenYang
China	Tianjin Cancer Hospital; Surgical Department	Tianjin City
China	The First Affiliated Hospital of Xi'an Jiaotong University; Hepatobiliary surgery Department	Xi'an
China	Xi'an Inernational Medical Center Hospital	Xi'an
China	Zhejiang Cancer Hospital	Zhejiang
China	Henan Cancer Hospital	Zhengzhou
China	Zhuhai People's Hospital	Zhuhai
Japan	Aichi Cancer Center	Aichi
Japan	Chiba University Hospital	Chiba
Japan	Kurume University Hospital	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kitasato University Hospital	Kanagawa
Japan	Yokohama City University Medical Center	Kanagawa
Japan	Kindai University Hospital	Osaka
Japan	Osaka University Hospital	Osaka
Japan	Toranomon Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

China,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TACE Progression-Free Survival (TACE PFS) as Determined by Investigator	TACE PFS is defined as the time from randomization to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first, as determined by the investigator (INV).	Randomization to untreatable progression or TACE failure/refractoriness or death (up to approximately 46 months)
Primary	Overall Survival (OS)	Overall survival (OS) after enrollment is defined as the time from randomization to death from any cause.	Randomization to death from any cause (up to approximately 94 months)
Secondary	Time to Untreatable (unTACEable) Progression (TTUP) as Determined by Investigator	INV-assessed TTUP is defined as time from randomization to untreatable (unTACEable) progression, as determined by investigator.	Randomization to untreatable (unTACEable) progression (up to approximately 46 months)
Secondary	Time to Progression (TTP) as Determined by Investigator	INV-assessed TTP is defined as the time from randomization to unTACEable progression or TACE failure/refractoriness (as defined above), as determined by investigator.	Randomization to unTACEable progression or TACE failure/refractoriness (up to approximately 46 months)
Secondary	Time to Extrahepatic Spread (EHS) as Determined by Investigator	INV-assessed time to EHS is defined as the time from randomization to the first evidence of EHS, as determined by investigator.	Randomization to first evidence of EHS (up to approximately 46 months)
Secondary	Objective Response Rate (ORR), as Determined by Investigator	Objective response (OR) is defined as a complete or partial response, as determined by investigator.	Randomization up to approximately 46 months
Secondary	Duration of Responses (DOR) as Determined by Investigator	INV-assessed DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by INV.	First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 46 months)
Secondary	Time to Deterioration (TTD)	TTD is defined as the time from randomization to first deterioration in the patient-reported GHS/QoL, physical function, or role function scales of the EORTC QLQ-C30, maintained for two consecutive assessments, or one assessment followed by death from any cause within 3 weeks.	Randomization to first deterioration (up to approximately 94 months)
Secondary	Percentage of Participants With Adverse Events		Baseline up to approximately 94 months