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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05992220
Other study ID # KCT0007365
Secondary ID KCT0007365
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 22, 2022
Est. completion date March 2026

Study information

Verified date August 2023
Source Asan Medical Center
Contact Jihyun An
Phone 82-31-560-2209
Email starlit1@naver.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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).


Recruitment information / eligibility

Status Recruiting
Enrollment 138
Est. completion date March 2026
Est. primary completion date March 2026
Accepts healthy volunteers No
Gender All
Age group 20 Years to 79 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Radiation:
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.
Drug:
Atezolizumab plus bevacizumab
Atezolizumab plus bevacizumab q3w

Locations

Country Name City State
Korea, Republic of Asan Medical Center Seoul

Sponsors (4)

Lead Sponsor Collaborator
Asan Medical Center Hanyang University, Seoul National University Hospital, Soon Chun Hyang University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Overall survival rate Randomization to death from any cause, through the end of study up to approximately 3 years
Secondary Objective response complete response or partial response as determined by the Investigator according to RECIST V1.1 up to approximately 3 years
Secondary Adverse reaction rate Adverse reaction rate assessed by CTCAE version 5 through study completion, up to approximately 3 years
Secondary Time to deterioration The time from randomization to first deterioration (decrease from baseline of =10 points) in the patient-reported global health status (GHS) / Quality of life (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 through study completion, up to approximately 3 years
Secondary Duration of response the time interval from the date of first occurrence of a documented objective response (CR or PR, whichever status is recorded first) until the first date that disease progression or death is documented, whichever occurs first. DOR will be assessed in patients who had an objective response. up to approximately 3 years
Secondary Tumor marker response (AFP, PIVKA-II) The decrease of >20% in serum concentration of each marker from baseline across all time points during study period. through study completion, up to approximately 3 years
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