Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion

NCT ID: NCT05992220

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-22
• Study Completion Date: 2026-03-31

Brief Summary

The recent global IMbrave150 study evaluated the combination of atezolizumab and bevacizumab versus sorafenib in 501 patients with advanced or metastatic Hepatocellular Carcinoma (HCC). The median overall survival (OS) was notably better in the atezolizumab/bevacizumab group. However, for HCC patients with intrahepatic macrovascular invasion (MVI), the prognosis remains poor, indicating a significant unmet need in this group.

External Beam Radiotherapy (EBRT) has shown promising results in treating HCC with MVI, especially when used in combination with trans-arterial chemoembolization (TACE). It has been reported that radiotherapy may make tumor cells more susceptible to immune-mediated therapy, potentially enhancing the effects of atezolizumab and bevacizumab.

Thus, this study aims to investigate the efficacy and safety of atezolizumab/bevacizumab alone versus atezolizumab/bevacizumab in combination with EBRT in HCC patients with macrovascular invasion.

Detailed Description

A total of 138 subjects are randomly assigned to one of two treatment groups (69 patients in the atezolizumab+bevacizumab group and 69 patients in the Atezolizumab plus Bevacizumab combined EBRT group).

• Radiotherapy combination:

• Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
• Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.
• The external beam radiotherapy will commence after day 2 of the first cycle of Atezolizumab+Bevacizumab, and will be delivered in accordance with institutional protocol.
• Atezolizumab+Bevacizumab:

• Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
• Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.

Additional study identifiers: This study was also registered on the WHO's International Clinical Trials Registry Platform, CRIS, before the first participant was enrolled (ID: KCT0007365, Date of registration: 2022-06-08).

Conditions

Hepatocellular Carcinoma; Hepatocellular Cancer; Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Stage IV; Liver Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy combination

Atezolizumab+Bevacizumab, combined EBRT to vascular invasion

• Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
• Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.
• The external beam radiotherapy will commence after day 2 of the first cycle of A+B, and will be delivered in accordance with institutional protocol.

Group Type: EXPERIMENTAL

Atezolizumab plus bevacizumab, combined EBRT to vascular invasion

Intervention Type: RADIATION

The external beam radiotherapy will commence after day 2 of the first cycle of atezolizumab+bevacizumab, and will be delivered in accordance with institutional protocol.

3D-conformal radiotherapy technique is used to determine target volumes, radiation ports, and dose prescriptions by using a 3D radiotherapy planning system.

The gross tumor volume (GTV) includes vascular invasion and a 2-cm margin into the contiguous HCC. The GTV can consist of the entire HCC and vascular invasion at the discretion of the investigator.

The target dose is 45 Gy, however, the total dose can be reduced as low as 30 Gy according to the liver function, liver volumes, or the maximum dose to the stomach/duodenum during the planning process according to the judgment of the radiation oncologist of each participating sites.

Atezolizumab+Bevacizumab

• Atezolizumab will be administered by IV, 1200 mg on day 1 of each 21day cycle.
• Bevacizumab will be administered by IV, 15 mg/kg on day 1 of each 21day cycle.

Group Type: ACTIVE_COMPARATOR

Atezolizumab plus bevacizumab

Intervention Type: DRUG

Atezolizumab plus bevacizumab q3w

Interventions

Atezolizumab plus bevacizumab, combined EBRT to vascular invasion

The external beam radiotherapy will commence after day 2 of the first cycle of atezolizumab+bevacizumab, and will be delivered in accordance with institutional protocol.

3D-conformal radiotherapy technique is used to determine target volumes, radiation ports, and dose prescriptions by using a 3D radiotherapy planning system.

The gross tumor volume (GTV) includes vascular invasion and a 2-cm margin into the contiguous HCC. The GTV can consist of the entire HCC and vascular invasion at the discretion of the investigator.

The target dose is 45 Gy, however, the total dose can be reduced as low as 30 Gy according to the liver function, liver volumes, or the maximum dose to the stomach/duodenum during the planning process according to the judgment of the radiation oncologist of each participating sites.

Intervention Type: RADIATION

Atezolizumab plus bevacizumab

Atezolizumab plus bevacizumab q3w

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Older than 19 years of age, lower than 80 years of age
• Child-Pugh class A hepatic function
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
• Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
• No prior systemic therapy for HCC
• At least one measurable HCC lesion with ≥ 1cm diameter
• Adequate hematologic and organ function

• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1,000 /mm3
• Platelet ≥ 50,000/ mm3 without transfusion
• Total bilirubin ≤ 2.5 mg/dL

Exclusion Criteria

• Treatment history of prior systemic treatment of HCC
• Liver transplant recipients
• Patients with peptic ulcer, untreated or incompletely treated varices with bleeding or high-risk for bleeding
• Any serious illness (e.g., active infection or inflammatory condition) or uncontrolled severe medical comorbidity
• A history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years
• Abdominal/pelvic radiotherapy within 28 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: collaborator

Hanyang University

OTHER

Sponsor Role: collaborator

Soon Chun Hyang University

OTHER

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Ju Hyun Shim

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ju Hyun Shim

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center

Locations

Asan Medical Center

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Jihyun An

Role: CONTACT

starlit1@naver.com

82-31-560-2209

Ju Hyun Shim

Role: CONTACT

s5854@amc.seoul.kr

Facility Contacts

Ju Hyun Shim

Role: primary

Other Identifiers

KCT0007365

Identifier Type: REGISTRY

Identifier Source: secondary_id

KCT0007365

Identifier Type: -

Identifier Source: org_study_id