Clinical trial NCT05992220: Atezolizumab Plus Bevacizumab Alone or Combined with External Beam Radiotherapy for HCC with Macrovascular Invasion
Official title: A Randomized, Multicenter, Open-Label, Phase II Trial of Atezolizumab Plus Bevacizumab Alone or Combined with External Beam RadioTherapy for HepatoCellular Carcinoma with Macrovascular Invasion (ALERT-HCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Seoul National University Hospital
name: Hanyang University
name: Soon Chun Hyang University
First posted: 2023-08-15
Enrollment: 138
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, multicenter, open-label study
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: progression-free survival rate
timeFrame: up to approximately 3 years
Secondary outcomes:
measure: Overall survival rate
timeFrame: up to approximately 3 years
measure: Objective response
timeFrame: up to approximately 3 years
measure: Adverse reaction rate
timeFrame: through study completion, up to approximately 3 years
measure: Time to deterioration
timeFrame: through study completion, up to approximately 3 years
measure: Duration of response
timeFrame: up to approximately 3 years
measure: Tumor marker response (AFP, PIVKA-II)
timeFrame: through study completion, up to approximately 3 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Ju Hyun Shim
role: PRINCIPAL_INVESTIGATOR
References: