Atezolizumab Plus Bevacizumab Alone or Combined With External Beam Radiotherapy for HCC With Macrovascular Invasion (ALERT-HCC)
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)
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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).
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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.
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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).
연구 유형
연구 유형
등록 (실제)
등록
단계
단계
- 2 단계
연락처 및 위치
연구 장소
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Seoul, 대한민국
- Asan Medical Center
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
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Older than 19 years of age, lower than 80 years of age
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Child-Pugh class A hepatic function
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
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Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
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No prior systemic therapy for HCC
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At least one measurable HCC lesion with ≥ 1cm diameter
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Adequate hematologic and organ function
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1,000 /mm3
- Platelet ≥ 50,000/ mm3 without transfusion
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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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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실험적: Radiotherapy combination
Atezolizumab+Bevacizumab, combined EBRT to vascular invasion
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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. |
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활성 비교기: Atezolizumab+Bevacizumab
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Atezolizumab plus bevacizumab q3w |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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progression-free survival rate
기간: up to approximately 3 years
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Randomization to the first occurrence of disease progression or death from any cause, whichever occurs first |
up to approximately 3 years
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Overall survival rate
기간: up to approximately 3 years
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Randomization to death from any cause, through the end of study |
up to approximately 3 years
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Objective response
기간: up to approximately 3 years
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complete response or partial response as determined by the Investigator according to RECIST V1.1 |
up to approximately 3 years
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Adverse reaction rate
기간: through study completion, up to approximately 3 years
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Adverse reaction rate assessed by CTCAE version 5 |
through study completion, up to approximately 3 years
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Time to deterioration
기간: through study completion, up to approximately 3 years
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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
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Duration of response
기간: up to approximately 3 years
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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
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Tumor marker response (AFP, PIVKA-II)
기간: through study completion, up to approximately 3 years
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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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공동 작업자 및 조사자
협력자
협력자
수사관
수사관
- 수석 연구원: Ju Hyun Shim, Asan Medical Center
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (실제)
기본 완료
연구 완료 (실제)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- KCT0007365
- KCT0007365 (레지스트리 식별자: CRIS (International Clinical Trials Registry Platform))
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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