Hepatic Arterial Infusion Chemotherapy Combined With Sintilimab and Bevacizumab in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Single-Center, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Response Rate
研究概览
简要总结
Primary liver cancer is the sixth most common cancer worldwide, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, of which intrahepatic cholangiocarcinoma accounts for 10%-15%. Surgical resection is the only curative method for ICC, but most patients are diagnosed at an advanced stage, and only 15% of patients can undergo surgical resection. In locally advanced ICC patients without distant metastases, although the tumor was initially assessed as unresectable, these patients may have the opportunity for surgical resection after reducing the size tumor lesion and increasing the remnant liver volume through conversion therapy. The current standard first-line treatment for unresectable ICC is gemcitabine combined with cisplatin, with a median overall survival of only 11.7 months and an ORR of 26.1%. In view of the poor effect of the standard chemotherapy regimen, the NCCN guidelines recommend that patients could participate in clinical study. Hepatic arterial infusion chemotherapy can increase the local blood drug concentration and improve the tumor regression rate. By reducing the dose of systemic chemotherapy drugs concentration, the incidence of adverse reactions can be reduced. Hepatic arterial infusion chemotherapy may be a better choice for locally advanced intrahepatic cholangiocarcinoma. PD-1 immunotherapy combined with targeted therapy is expected to improve the prognosis of patients with intrahepatic cholangiocarcinoma. This study investigates the safety and efficacy of hepatic arterial infusion chemotherapy combined with sintilimab and bevacizumabin the treatment of unresectable ICC.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ICC diagnosed by imaging examination (CT or MRI) and pathology;
- •ICC patient without any previous tumor treatment
- •The tumor was assessed as unresectable by two liver surgeons. Any of the following conditions: (1) Residual liver volume less than 30-40%; (2) Not possible for R0 radical resection; (3) Tumor invades the portal vein, hepatic artery and bile duct, and the normal residual liver cannot be guaranteed blood supply and bile drainage; the tumor involves the hepatic veins and cannot preserve at least one vein.
- •At least one assessable intrahepatic lesion;
- •ECOG PS score 0-1;
- •Child-Pugh class A;
- •Life expectancy is at least 3 months;
- •Age between 18 and 75 years old;
- •Baseline laboratory tests meet the following criteria:
- •Neutrophils ≥1.5×10^9/L White blood cells ≥3.0×10^9/L Platelets ≥75×10^9/L Hemoglobin ≥80g/L Serum ALT, AST ≤ 3 x upper limit of normal (ULN) Serum creatinine ≤ 1.5 x ULN INR < 1.5, or prothrombin time < ULN+4 seconds Albumin ≥30g/L Total bilirubin ≤ 3 x upper limit of normal (ULN)
排除标准
- •Distant metastasis;
- •Refused to receive PD-1 inhibitor and apatinib treatment;
- •Any of the following conditions within the first 12 months of the study: myocardial infarction, severe/unstable angina, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack), Pulmonary embolism; ongoing: arrhythmia grade ≥2 according to NCI-CTCAE criteria, QTc prolongation (>450 ms in men, >470 ms in women);
- •Renal insufficiency requires peritoneal dialysis or hemodialysis;
- •Serious dysfunction of other important organs;
- •A second primary malignant tumor was diagnosed in the past;
- •Known or new evidence of brain or leptomeningeal lesions;
- •Hemophilia or bleeding tendency, who are taking anticoagulation therapy such as coumarin derivatives in therapeutic doses;
- •Pregnant or lactating women, all female patients of childbearing potential must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative;
- •History of previous organ transplantation;
- •Known HIV infection;
- •Allergy to chemotherapy drugs;
- •Patients with other serious acute or chronic physical or psychiatric diseases or abnormal laboratory tests that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results or the investigators consider unsuitable for enrollment.
研究组 & 干预措施
HAIC Combined with Sintilimab and Bevacizumab
干预措施: HAIC Combined with Tislelizumab and Apatinib (Drug)
结局指标
主要结局
Response Rate
时间窗: 12 months
The objective response rate was calculated according to the RECIST 1.1.
次要结局
- Conversion rate to resection(12 months)
- Overall Survival time(12 months)
- Disease Control Rate(12 months)
- Progression-free survival(12 months)
研究者
Binkui Li
Professor
Sun Yat-sen University