Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion
- Conditions
- Liver CancerHepatocellular Carcinoma Stage IVHepatocellular CarcinomaHepatocellular CancerHepatocellular Carcinoma Non-resectable
- Interventions
- Radiation: Atezolizumab plus bevacizumab, combined EBRT to vascular invasion
- Registration Number
- NCT05992220
- Lead Sponsor
- Asan Medical Center
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 138
-
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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atezolizumab+Bevacizumab Atezolizumab plus 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. Radiotherapy combination Atezolizumab plus bevacizumab, combined EBRT to vascular invasion 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.
- Primary Outcome Measures
Name Time Method progression-free survival rate up to approximately 3 years Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first
- Secondary Outcome Measures
Name Time Method Time to deterioration through study completion, up to approximately 3 years 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
Objective response up to approximately 3 years complete response or partial response as determined by the Investigator according to RECIST V1.1
Adverse reaction rate through study completion, up to approximately 3 years Adverse reaction rate assessed by CTCAE version 5
Tumor marker response (AFP, PIVKA-II) through study completion, up to approximately 3 years The decrease of \>20% in serum concentration of each marker from baseline across all time points during study period.
Overall survival rate up to approximately 3 years Randomization to death from any cause, through the end of study
Duration of response up to approximately 3 years 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.
Trial Locations
- Locations (1)
Asan Medical Center
🇰🇷Seoul, Korea, Republic of