Downstaging of Hepatocellular Carcinoma with Macrovascular Invasion by Radiotherapy (SBRT or Y90) and Atezolizumab Plus Bevacizumab Followed by Liver Transplantation - a Prospective Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Evaluate Downstaging Efficacy
研究概览
简要总结
The goal of this clinical trial is to learn if locoregional therapy and immunotherapy can be used together to help patients with hepatocellular carcinoma (HCC) and macrovascular invasion achieve liver transplantation.
The main questions it aims to answer are:
- How many patients will achieve transplant with this treatment strategy?
- What will the 5-year survival and recurrence-free survival rates be for these patients?
Participants will:
- Undergo a biopsy of the tumor.
- Receive locoregional therapy (SBRT or Y90) followed by immunotherapy (atezolizumab and bevacizumab) 2 to 6 weeks later, for a maximum of 9 months.
- Be referred for a liver transplant and undergo the procedure if deemed eligible and safe.
- If applicable, be followed for five years post-transplant with regular data collection.
详细描述
This is a pilot, open-label, single-arm, study evaluating the combination of locoregional radiotherapy (SBRT or Y90-RE) followed by Atezolizumab and Bevacizumab (AtezoBev) in patients with advanced liver cancer. The study aims to assess the feasibility of integrating immunotherapy with locoregional treatments and liver transplantation pathways.
Disease Background:
Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer, globally the 6th most common cancer, 3rd leading cause of cancer-related deaths with a stage-dependent detrimental poor prognosis. In 2023 in Canada 4,700 patients were diagnosed with liver cancers with an overall 5 year survival of 45% (95%CI 42, 47).
HCC is a well vascularized tumor and may complicate by invading the surrounding vascular structures. If this invasion is identified on imaging or pathology, this is called macrovascular invasion (MVI). In case of MVI, it is most commonly seen affecting the portal vein (PV) and less commonly the hepatic vein (HV), inferior vena cava (IVC) or hepatic artery (HA). With regard to localization of MVI of the PV and its branches, a classification (Vp1-Vp4) has been published to harmonize reporting and to facilitate the clinical decision-making process. As an additional comorbidity of an MVI affecting the PV, an adjacent portal vein tumor thrombus (PVTT) may further deteriorate the hepatic function. Overall MVI in HCC is detected in ~35% of patients at time of diagnosis6. In this subgroup of patients, a 3-year overall survival (OS) of 20% (95%CI 0.13, 0.26) has been reported.
In general, for patients with HCC, numerous guidelines and recommendations for diagnostics, staging, and management are available and updated regularly including those from the 'European Association for the Study of the Liver' (EASL) and the 'American Association for the Study of Liver Diseases' (AASLD). Among most guidelines, the commonly recommended staging criteria is the Barcelona Clinic Liver Cancer (BCLC) classification. Clinical decision making for the optimal treatment is guided by the BCLC tumor stages. According to BCLC, HCC with MVI is classified as advanced disease (BCLC stage C).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70
- •Weight > 30 kg
- •Child Pugh Turcotte score A5 to B7
- •Macrovascular invasion (Vp1-3)
- •Total tumour volume < 350 cm3
- •Alpha Fetoprotein < 5000 ng/mL
- •No extrahepatic disease
- •No other contraindications to undergo a LT
- •Eastern Cooperative Oncology Group (ECOG) score 0-1
- •Capable to provide inform consent
- •Radiological and histological confirmation of hepatocellular carcinoma
排除标准
- •Poorly differentiated HCC
- •Prior therapy for hepatocellular carcinoma other than liver resection or ablation
- •Portal vein tumor thrombus extending beyond main portal vein
- •Obesity class III (BMI ≥ 40 kg/m2)
- •Contraindications for radiotherapy (Y90 or SBRT) or AtezoBev
研究组 & 干预措施
Treatment
This is a pilot, single-arm study enrolling 48 patients to evaluate the feasibility of locoregional therapy followed by immunotherapy in patients with advanced liver cancer. Patients will receive stereotactic body radiotherapy or Yttrium-90 radioembolization as per the standard-of-care (SOC) protocol, determined during Multidisciplinary Rounds.
Starting two to six weeks after radiotherapy, patients will begin treatment with Atezolizumab and Bevacizumab administered in approximately 21-day intervals, following SOC procedures, for a maximum of 9 months. Clinical follow-up will align with SOC protocols, and imaging will be performed every 2-3 months during immunotherapy.
If a patient is sufficiently responding to treatment at any follow-up, patients will be referred for transplant evaluation and added to the waitlist if no contraindications are found. Patients with disease progression or who become ineligible for LT due to other factors will be transitioned off the study.
干预措施: Atezolizumab & Bevacizumab (Biological)
Treatment
This is a pilot, single-arm study enrolling 48 patients to evaluate the feasibility of locoregional therapy followed by immunotherapy in patients with advanced liver cancer. Patients will receive stereotactic body radiotherapy or Yttrium-90 radioembolization as per the standard-of-care (SOC) protocol, determined during Multidisciplinary Rounds.
Starting two to six weeks after radiotherapy, patients will begin treatment with Atezolizumab and Bevacizumab administered in approximately 21-day intervals, following SOC procedures, for a maximum of 9 months. Clinical follow-up will align with SOC protocols, and imaging will be performed every 2-3 months during immunotherapy.
If a patient is sufficiently responding to treatment at any follow-up, patients will be referred for transplant evaluation and added to the waitlist if no contraindications are found. Patients with disease progression or who become ineligible for LT due to other factors will be transitioned off the study.
干预措施: Yttrium-90 (Y-90) (Drug)
Treatment
This is a pilot, single-arm study enrolling 48 patients to evaluate the feasibility of locoregional therapy followed by immunotherapy in patients with advanced liver cancer. Patients will receive stereotactic body radiotherapy or Yttrium-90 radioembolization as per the standard-of-care (SOC) protocol, determined during Multidisciplinary Rounds.
Starting two to six weeks after radiotherapy, patients will begin treatment with Atezolizumab and Bevacizumab administered in approximately 21-day intervals, following SOC procedures, for a maximum of 9 months. Clinical follow-up will align with SOC protocols, and imaging will be performed every 2-3 months during immunotherapy.
If a patient is sufficiently responding to treatment at any follow-up, patients will be referred for transplant evaluation and added to the waitlist if no contraindications are found. Patients with disease progression or who become ineligible for LT due to other factors will be transitioned off the study.
干预措施: Stereotactic body radiotherapy (SBRT) (Radiation)
结局指标
主要结局
Evaluate Downstaging Efficacy
时间窗: From enrollment to liver transplantation.
The number of patients who achieve a liver transplant.
次要结局
- Long-term Oncological Results(Form enrollment to 5 years post-transplant.)
研究者
Gonzalo Sapisochin
LeGresley Chair in Transplant Oncology at UHN, Associate Professor of Surgery Abdominal Transplant & HPB Surgical Oncology
University Health Network, Toronto