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| ID | Type | Description | Link |
|---|---|---|---|
| KCT0007365 | Registry Identifier | CRIS (International Clinical Trials Registry Platform) |
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| Name | Class |
|---|---|
| Seoul National University Hospital | OTHER |
| Hanyang University Guri Hospital | OTHER |
| Soon Chun Hyang University | OTHER |
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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.
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+Bevacizumab:
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Radiotherapy combination | Experimental | Atezolizumab+Bevacizumab, combined EBRT to vascular invasion
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| Atezolizumab+Bevacizumab | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival rate | Randomization to death from any cause, through the end of study | up to approximately 3 years |
| Objective response | complete response or partial response as determined by the Investigator according to RECIST V1.1 |
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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
Total bilirubin ≤ 2.5 mg/dL
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jihyun An | Contact | 82-31-560-2209 | starlit1@naver.com | |
| Ju Hyun Shim | Contact | s5854@amc.seoul.kr |
| Name | Affiliation | Role |
|---|---|---|
| Ju Hyun Shim | Asan Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center | Recruiting | Seoul | South Korea |
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randomized, multicenter, open-label study
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| Atezolizumab plus bevacizumab | Drug | Atezolizumab plus bevacizumab q3w |
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| up to approximately 3 years |
| Adverse reaction rate | Adverse reaction rate assessed by CTCAE version 5 | through study completion, up to approximately 3 years |
| 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 |
| 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 |
| 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 |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D008113 | Liver Neoplasms |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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