Efficacy and Safety of Low-Dose Bevacizumab and Atezolizumab Combined With Transarterial Chemoembolization Sequential Hepatic Arterial Infusion Chemotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Single-Arm, Phase II Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 38
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a prospective, single-arm, phase II clinical study designed to evaluate the efficacy and safety of low-dose bevacizumab plus atezolizumab combined with transarterial chemoembolization followed by hepatic arterial infusion chemotherapy (TACE-HAIC) as first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). The study plans to enroll approximately 38 patients with unresectable, locally advanced HCC who have not received prior systemic therapy.
Although atezolizumab plus bevacizumab has become a standard first-line treatment option for advanced HCC, the objective response rate remains limited. TACE-HAIC may improve tumor control by increasing local chemotherapy exposure, promoting tumor antigen release, and enhancing the anti-tumor activity of immunotherapy and anti-angiogenic therapy. In this study, patients will receive TACE-HAIC in combination with atezolizumab and low-dose bevacizumab, followed by maintenance treatment with atezolizumab plus low-dose bevacizumab until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria.
The primary endpoint is objective response rate (ORR) assessed by investigators according to RECIST version 1.1. Secondary endpoints include ORR by mRECIST, disease control rate, duration of response, progression-free survival, time to progression, overall survival, and safety. This study aims to explore whether this combination strategy can provide improved anti-tumor activity with manageable safety in patients with unresectable HCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily provides written informed consent. Age ≥18 years. Histologically or cytologically confirmed hepatocellular carcinoma (HCC), or clinically diagnosed HCC in patients with cirrhosis according to AASLD criteria.
- •Unresectable HCC suitable for TACE treatment, including BCLC stage B or C, without Vp4 portal vein tumor thrombus or extrahepatic metastasis.
- •No prior systemic therapy for HCC. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Child-Pugh class A or class B7 liver function. No history of autoimmune disease. Life expectancy of at least 3 months. At least one measurable lesion according to RECIST v1.
- •Adequate hematologic, hepatic, and renal function within 1 week before enrollment:
- •Neutrophils ≥1.5 × 10^9/L Platelets ≥50 × 10^9/L Hemoglobin ≥90 g/L ALT and AST ≤5 × upper limit of normal (ULN) Serum creatinine ≤1.5 × ULN INR <2.3, or prothrombin time ≤ULN + 6 seconds Albumin ≥30 g/L Total bilirubin ≤3 × ULN Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment, must not be breastfeeding, and must agree to use effective contraception during the study and for 6 months after the end of study treatment. Men must also agree to use effective contraception during the study and for 6 months after the end of study treatment.
排除标准
- •Known intrahepatic cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma, or fibrolamellar carcinoma; or other active malignancy within 5 years, except adequately treated localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervix, or breast.
- •Severe allergy to iodinated contrast agents that precludes TACE-HAIC treatment. Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 1 month before enrollment.
- •Active infection that cannot be effectively controlled. Severe gastroesophageal varices, or untreated/incompletely treated varices with bleeding or high bleeding risk.
- •Brain metastases or bone metastases requiring urgent surgical or radiotherapeutic intervention.
- •Pregnancy, suspected pregnancy, or breastfeeding. Current use of, or recent use within 10 days before study treatment of, aspirin >325 mg/day, dipyridamole, ticlopidine, clopidogrel, or cilostazol.
- •Thrombotic or embolic events within 6 months before treatment initiation, including cerebrovascular accident, transient ischemic attack, cerebral hemorrhage, cerebral infarction, or pulmonary embolism.
- •Congenital or acquired immunodeficiency. Any of the following within 12 months before study start: myocardial infarction, severe or unstable angina, or congestive heart failure.
- •Renal failure requiring dialysis. Prior organ transplantation. Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality, that may increase study risk, interfere with interpretation of results, or make the patient unsuitable for enrollment in the investigator's judgment.
研究组 & 干预措施
TACE-HAIC + Atezolizumab + Low-dose Bevacizumab
Participants with unresectable hepatocellular carcinoma who have not received prior systemic therapy will be enrolled into a single treatment cohort. All participants will receive transarterial chemoembolization followed by hepatic arterial infusion chemotherapy (TACE-HAIC) in combination with atezolizumab and low-dose bevacizumab as first-line treatment. Atezolizumab will be administered at a fixed dose of 1200 mg intravenously every 3 weeks, and bevacizumab will be administered at 7.5 mg/kg intravenously every 3 weeks. HAIC will be given using the FOLFOX regimen, and subsequent TACE will be performed as needed according to the patient's condition and investigator judgment. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, conversion to resectable disease, or other protocol-defined discontinuation criteria.
干预措施: TACE-HAIC + Atezolizumab + Low-dose Bevacizumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 2 years
Percentage of participants achieving complete response (CR) or partial response (PR) as best overall response (BOR) according to RECIST v1.1 criteria, assessed by the investigator.
Progression-Free Survival (PFS)
时间窗: 2 years
PFS is defined as the time from the first dose of study treatment to the first documented disease progression per RECIST v1.1 criteria or death from any cause, whichever occurs first, as assessed by the investigator.
次要结局
未报告次要终点
研究者
Huang Mingsheng
The director of Department of Interventional Radiology
Third Affiliated Hospital, Sun Yat-Sen University