주요 포털 정맥 혈전증을 가진 HCC의 면역 요법 및 Atezo-Bev와 SBRT
고급 HCC 및 주요 문맥 정맥 종양 혈전증 환자에서 면역 요법 (Atezolizumab + Bevacizumab)을 이용한 전형적인 신체 방사선 요법
Patients with PVTT involvement is a significant healthcare burden as they are present in up to 40% of patients with HCC at diagnosis. These patients exhibit a poorer prognosis compared to patients without PVTT, as a result they were often excluded from existing pivotal clinical trials [9-11]. Without management, the median OS in affected patients could be as short as 2 to 4 months. The role of liver-directed therapies is limited for patients with major PVTT. For example, percutaneous ablation to PVTT is technically challenging, especially for centrally located PVTT due to their proximity to hepatic vasculature and bile ducts. Transarterial therapies are contraindicated for patients with major PVTT due to risk of concurrent interruption of both hepatic arterial and portal venous blood flow resulting in severe liver ischemia. Therefore, patients with major PVTT are recommended to receive systemic treatment by international guidelines. Yet, the OS for patients with main PVTT remained poor. In the exploratory analysis of IMbrave-150, patients with main PVTT who received atezolizumab plus bevacizumab had a median OS of 7.6 months only, compared to 21.1 months for those without PVTT. There is a huge unmet for this group of patients with dismal prognosis.
SBRT is a radiotherapy technique that enables delivery of high dose of radiation in an extremely precise manner. Compared to more conventional radiotherapy techniques such as intensity modulated radiotherapy (IMRT), SBRT has the advantage of superior disease control, minimizing dose to normal tissue and toxicity, and reduction of overall treatment time. For patients with PVTT, a number of retrospective and prospective trials have shown that SBRT can offer durable local control for patients with PVTT involvement. For instance, a randomized trial conducted in Korean which compared the combination of TACE-radiation (TACE-RT) with sorafenib, involving 90 patients with Child-Pugh A HCC with macrovascular invasion (MVI) (35% had main or bilateral portal vein involvement), showed improved 12-week PFS (86.7% vs. 34.3%), time-to-progression (31.0 vs. 11.7 weeks; p<0.001), and OS (55.0 vs. 43.0 weeks; p=0.04) with TACE-RT. In a Canadian single-center retrospective study including 128 patients with HCC and MVI treated with SBRT between 2003 to 2016, 1-year local control was 87.4% and median OS was 18.3 months.
Given the existing evidence, it would be of interest to study the efficacy and safety of atezolizumab plus bevacizumab and SBRT to portal venous tumour thrombosis in this patient group.
연구 개요
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Landon CHAN
- 전화번호: 3505 1042
- 이메일: landon.chan@cuhk.edu.hk
연구 연락처 백업
- 이름: Natalie KWONG
- 전화번호: 3505 1040
- 이메일: nataliekwong019@cuhk.edu.hk
연구 장소
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Hong Kong, 홍콩
- 모병
- Department of Clinical Oncology, Prince of Wales Hospital
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연락하다:
- Natalie KWONG
- 전화번호: 3505 1040
- 이메일: nataliekwong019@cuhk.edu.hk
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연락하다:
- Landon L CHAN
- 전화번호: 3505 1042
- 이메일: landon.chan@cuhk.edu.hk
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수석 연구원:
- Landon L CHAN
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Hong Kong, 홍콩
- 모병
- Department of Clinical Oncology, Tuen Mun Hospital
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연락하다:
- Natalie SM WONG
- 전화번호: 2468 5088
- 이메일: wsm011@ha.org.hk
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연락하다:
- Jay JJ Huang
- 전화번호: 2468 5088
- 이메일: hjj732@ha.org.hk
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수석 연구원:
- Natalie SM WONG
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Patients aged ≥ 18 years old
- ECOG performance 0 to 1
- Confirmed diagnosis of HCC (either histologic or cytologic analysis, or clinical features according to the American Association for the Study of Liver Diseases)
- Presence of major portal vein thrombosis (Vp3 [first-order tumour thrombosis in portal vein] or Vp4 [tumour thrombosis in the main portal vein, or portal vein branch in contralateral lobe]), limited to the liver and should be amenable to SBRT
- Presence of ≤5 lesions within the liver
- Gastric or esophageal varices must be screened; if interventions were performed, repeated upper endoscopy is needed to confirm healing of treated varices
- Child-Pugh A liver function
- Life expectancy longer than 3 months
- At least one measurable treatment lesion according to RECIST 1.1
- Extrahepatic metastases are allowed, limited to 3 sites, and not causing functional compromise
- Written informed consent must be obtained prior to any study related procedures
- Adequate haematological function (Hb ≥ 8.5g/dL; Plt ≥ 75x10^9/L; ANC ≥ 1.5x10^9/L; INR ≤ 1.5)
- Adequate hepatic function (albumin ≥ 28g/L; Bilirubin ≤ 40 μmol/L; ALT < 5 times upper limit normal)
- Adequate renal function (serum creatinine ≤ 2 times the upper limit of normal range; Na ≥ 130mmol/L; K ≥ 3.0mmol/L)
- Able to read, understand and provide written consent
Exclusion Criteria:
- History of another malignancy except appropriately-treated BCC of skin or CIN of cervix during the last 5 years
- History of rupture HCC in the past 3 months
- History of gastric or esophageal varices with interventions performed within 1 month
- Tumour thrombosis that extends beyond the portal vein (e.g. inferior vena cava, superior vena cava)
- Liver tumours occupy ≥ 50% of liver
- Previous radiotherapy to the abdomen
- Previous yttrium-90 chemoembolization
- Repetitive history of non-healing wounds or ulcers within 2 months of inclusion
- Pregnant or lactating females at any time during the study
- Active autoimmune disease requiring systemic therapy in the past 2 years
- Diagnosis of immunodeficiency (including HIV)
- Ongoing corticosteroid therapy >10mg prednisone daily
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Receiving Atezolizumab + Bevacizumab and SBRT
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- SBRT 27.5Gy to 50Gy in 5 fractions on alternate days will be delivered between cycle 3 and 5 to the PVTT and its adjacent lesions.
다른 이름들:
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다른: Standard of care Atezolizumab + Bevacizumab alone (Control arm)
- In the control arm, Atezolizumab 1200mg IV and Bevacizumab 15mg/kg IV will be given every 3 weeks, till disease progression, intolerable toxicity, death or withdrawal of consent. |
- Atezolizumab 1200mg IV and Bevacizumab 15mg/kg IV will be given every 3 weeks, till disease progression, intolerable toxicity, death or withdrawal of consent. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
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1 년 전체 생존 (OS)
기간: 1 년
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1 년
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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전체 생존 중앙값 (OS)
기간: 2 년
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2 년
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중간 무 진행 생존 (PFS)
기간: 2 년
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2 년
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객관적인 응답 속도 (Recist 1.1)
기간: 2 년
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2 년
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치료 관련 부작용
기간: 2 년
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2 년
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공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- HCC080
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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