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

NCT05992220 | Recruiting Phase 2 DMC

• 1 other identifier: KCT0007365
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

HCC; vascular invasion; portal vein tumor thrombosis; BCLC stage C

Outcome Measures

Primary Outcomes (1)

• progression-free survival rate

  Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first

  up to approximately 3 years

Secondary Outcomes (6)

• Overall survival rate

  up to approximately 3 years

• Objective response

  up to approximately 3 years

• Adverse reaction rate

  through study completion, up to approximately 3 years

• Time to deterioration

  through study completion, up to approximately 3 years

• Duration of response

  up to approximately 3 years

Study Arms (2)

Radiotherapy combination

EXPERIMENTAL

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.

Radiation: Atezolizumab plus bevacizumab, combined EBRT to vascular invasion

Atezolizumab+Bevacizumab

ACTIVE COMPARATOR

* 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.

Drug: Atezolizumab plus bevacizumab

Interventions

Atezolizumab plus bevacizumab, combined EBRT to vascular invasion 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.

Radiotherapy combination

Atezolizumab plus bevacizumab DRUG

Atezolizumab plus bevacizumab q3w

Atezolizumab+Bevacizumab

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead
• Seoul National University Hospital: collaborator
• Hanyang University Guri Hospital: collaborator
• Soon Chun Hyang University: collaborator

Study Sites (1)

Asan Medical Center

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ju Hyun Shim

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jihyun An

CONTACT

82-31-560-2209; starlit1@naver.com

Ju Hyun Shim

CONTACT

s5854@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: randomized, multicenter, open-label study

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 15, 2023
• Study Start: October 22, 2022
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 21, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)