Combination Therapy With Anti-angiogenic Agents and Anti-PD-1 Antibodies for Unresectable or Advanced Hepatocellular Carcinoma: a Cohort Study
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Objective response
研究概览
简要总结
Combination treatment with antiangiogenic agents and anti-programmed cell death protein 1 (PD-1) antibodies have shown high anti-tumor efficacy for patients with unresectable or advanced hepatocellular carcinoma (uHCC). In this single-center cohort study, we are aiming to (1) evaluate the clinical effectiveness in real-world patients, especially for Chinese patients, most of whom were with hepatitis B virus infection; (2) predict clinical effectiveness with clinicopathological features; (3) predict clinical effectiveness with histologic features and blood samples.
详细描述
Combination treatment with antiangiogenic agents and anti-programmed cell death protein 1 (PD-1) antibodies have shown high anti-tumor efficacy for patients with unresectable or advanced hepatocellular carcinoma (uHCC). In this single-center cohort study, we are aiming to:
- To evaluate the clinical effectiveness in real-world patients, especially for Chinese patients most of whom were with hepatitis B virus infection.
- To predict clinical effectiveness with clinicopathological features, such as lab examinations (at baseline and dynamic changes), radiological features (radiomics study at the baseline);
- To predict clinical effectiveness with histologic features, such as PD-L1 expression, ctDNA, and peripheral immune cell subtypes.
- To evaluate the clinical effectiveness of second- or third-line therapies, including TACE, HAIC, and interferon, for those who lost clinical benefit or who were intolerant to the combination therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of HCC confirmed by histology/cytology or clinical diagnosis of HCC by Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 edition) criteria.
- •Unresectable or advanced disease at the investigator's discretion. The advanced stage was BCLC C stage or China Liver Cancer Stage IIIa or IIIb.
- •Child-Pugh class A or B
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Subjects received combination therapy with an anti-angiogenic agent and an anti-PD-1/PD-L1 antibody, received at least one imaging evaluation, and signed an Informed Consent Form. Anti-angiogenic agents include sorafenib, lenvatinib, apatinib, and bevacizumab; anti-PD-1/PD-L1 antibodies include pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, tislelizumab, and atezolizumab.
- •Adequate hematologic and end-organ function.
排除标准
- •Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- •History of malignancy other than HCC within 5 years prior to the therapy, with the exception of adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or papillary thyroid carcinoma.
- •History of organ transplantation or hepatic encephalopathy.
- •Allergic to anti-angiogenic agents or anti-PD-1/PD-L1 agents.
- •History of gastrointestinal perforation and/or fistula within the 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea within 6 months.
- •Active autoimmune disease requiring systemic therapy within 2 years prior to the first dose, allowing the use of alternative therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency); history of primary immunodeficiency; presence of only autoimmune antibody-positive subjects. The presence of autoimmune disease needs to be confirmed at the investigator's discretion.
- •Uncontrollable hypertension, SBP >140 mmHg or DBP >90 mmHg after optimal medical therapy, hypertensive crisis, or history of hypertensive encephalopathy.
- •Subjects had a bleeding event in the past 6 months due to esophageal or gastric fundus varices induced by portal venous hypertension; subjects have undergone a gastrointestinal endoscopy within 3 months prior to the first dose to diagnose the presence of severe (G3) varices; subjects had a high risk of bleeding as assessed by the investigator.
- •Subject requests withdrawal of informed consent.
- •Other conditions that the investigator deems inappropriate for participation in this study.
研究组 & 干预措施
Combinational therapy
Participants who receive systemic treatment with an anti-angiogenic agent, including sorafenib, lenvatinib, apatinib, and bevacizumab, in combination with an anti-PD-1/PD-L1 antibody, including pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, tislelizumab, and atezolizumab.
干预措施: Anti-angiogenic agents plus anti-PD-1/PD-L1 antibodies (Drug)
结局指标
主要结局
Objective response
时间窗: up to 2 years
Subjects with complete response or partial response
次要结局
- Duration of response(up to 2 years)
- Time to deterioration in patient-reported quality of life, physical functioning, and role functioning(up to 2 years)
- Progression free survival(up to 2 years)
- Overall survival(up to 2 years)
- Ratio of R0 resection(up to 2 years)
- Recurrence-free survival(up to 5 years)
研究者
Hui-Chuan Sun
Professor of Surgery
Shanghai Zhongshan Hospital