Efficacy and Safety of SBRT Combined With Atezolizumab Plus Bevacizumab vs Atezolizumab Plus Bevacizumab in Treating Unresectable Advance Hepatocellular Carcinoma (SAB - A Prospective Observational Study).
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR), which is defined as the proportion of patients with complete response (CR) and partial response (PR) at 6 months . CR or PR is assessed in accordance with mRECIST.
研究概览
简要总结
SBRT, atezolizumab, and bevacizumab have different mechanisms of action and can potentially have synergistic effects when combined. SBRT delivers targeted radiation to the tumor, while atezolizumab enhances the immune response, and bevacizumab inhibits angiogenesis. The combination of SBRT with atezolizumab and bevacizumab will result in improved tumor response rates as compared to atezolizumab and bevacizumab alone in patients with advance unresectable hepatocellular carcinoma (HCC). Up until now, no study has been done that has compared SBRT with atezolizumab, and bevacizumab in unresectable advance hepatocellular carcinoma. In this study the patients will receive these above-mentioned treatments as a part of their treatment protocol. These treatments are not given under this study. However in our observational study, we aim to compare the efficacy and safety of SBRT combined with atezolizumab and bevacizumab versus atezolizumab and bevacizumab alone in the treatment of unresectable advance hepatocellular carcinoma (HCC).
Hypothesis: The combination of SBRT with atezolizumab and bevacizumab will result in improved tumor response rates as compared to atezolizumab and bevacizumab alone in patients with advance unresectable hepatocellular carcinoma (HCC).
AIM:- The aim of this study is to compare the efficacy and safety of SBRT combined with atezolizumab and bevacizumab versus atezolizumab and bevacizumab alone in the treatment of unresectable advance hepatocellular carcinoma (HCC).
Study design:
• A prospective observational study.
• Single Centre.
• Open label.
• The study will be conducted in Department of Hepatology, ILBS.
Study period: 1 years after ethical approval.
Sample size:
• Assuming that objective response rate with immunotherapy is 30%, further adding SBRT along with immunotherapy is increased by 50% that is objective response rate by adding SBRT is 80% .
• With âº-5 and power 80% we need to enroll 36 cases and further adding 10% dropout rate we need to enroll 40 cases i.e. 20 in each group.
Monitoring and assessment: All the parameters of the objective and also noted any adverse effects.
STATISTICAL ANALYSIS:
The continuous data will be represented as mean +/- SD or median (IQR). The categorical data will be represented as median (IQR).The comparison of continuous data will be done by using either Student’s t test or Mann -Whitney test as appropriate. The Kaplan Meier and Cox regression will be used for survival analysis. Besides this an appropriate analysis will be done at the time of data analysis. P value < 0.05 will be considered as significant.
研究设计
- 研究类型
- Observational
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Age 18–70 years.
- •Unresectable advance HCC with PVT
- •At least one measurable (measurable according to Response Evaluation Criteria In Solid Tumors (mRECIST untreated lesions.
- •Patients with hepatitis B virus (HBV) infection: HBV-DNA less than 500 IU per mL obtained within 28 days before the start of study treatment and received anti-HBV treatment for at least 28 days before entering the study.
- •Maximum diameter of tumor less than equals to 15cm
- •Maximum number of tumor nodules less than equals to 5
- •Liver function: Child-Pugh class A, B7; normal liver volume is more than 800cm
- •Karnofsky performance status more than equals to 80%
- •The expected survival of the patient is more than 6 months.
- •The following conditions are met: i.
- •Platelet more than equals to 60 per L; White blood cell more than equals to 3.0×109 per L; Hemoglobin more than equals to 85 g per L; Serum creatinine less than equals to 1.4 upper limit;.
- •PT-INR less than equals to 1.7.
排除标准
- •Patients with untreated or incompletely treated esophageal and or gastric varices with associated bleeding or at high risk of bleeding.
- •Coinfection with HBV and hepatitis C virus (HCV).
- •Symptomatic, untreated or progressively progressive central nervous system (CNS) metastases.
- •The patient cannot receive follow-up or is participating in other clinical trials.
- •Subjects deemed unsuitable for inclusion in this study by the investigator.
- •Current or past autoimmune disease or immunodeficiency.
- •History of leptomeningitis.
- •Idiopathic pulmonary fibrosis, organising pneumonia or evidence of active pneumonia on chest.
- •Known active tuberculosis.
- •Severe infection within 4 weeks prior to initiation of study treatment
- •A potential subject who meets any of the following criteria will be excluded from participation in this study: i) Previous radiotherapy to the liver ii) Known current pregnancy iii) Loss of fat planes of tumor with organ at risk like the esophagus, stomach, duodenum, small bowel on CT or on MRI.
结局指标
主要结局
Objective response rate (ORR), which is defined as the proportion of patients with complete response (CR) and partial response (PR) at 6 months . CR or PR is assessed in accordance with mRECIST.
时间窗: 6 months
次要结局
- Overall survival at 3, 6 and 12 months(3, 6 and 12 months)
- Disease control rate (DCR) at 3, 6 and 12 months, defined as the percentage of subjects with the best response as CR, PR or stable disease (SD)(3, 6 and 12 months)
- Progression-free survival (PFS) at 3, 6 and 12 months(3, 6 and 12 months)
- Adverse events 3, 6 and 12 months(3, 6 and 12 months)
- Biomarkers change( AFP , PIVKA II) at 3, 6 and 12 months(3, 6 and 12 months)
研究者
Dr Phool Chand
Institute of Liver and Biliary Sciences