Efficacy and Safety of Hepatic Artery Infusion Chemotherapy in Patients With Advanced or Unresectable Hepatocellular Carcinoma Who Have Progressed or Are Intolerant to Systemic Therapy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Objective response of intrahepatic lesions
研究概览
简要总结
There are limited treatment options for patients with unresectable hepatocellular carcinoma (HCC) who failed to the combination therapy with targeted agents plus anti-PD-1/PD-L1. Hepatic artery infusion chemotherapy (HAIC) had shown potent antitumor effects in single-centered studies when was used as first-line therapy. However, HAIC was not used as second or third-line therapy.
详细描述
The combination therapy of anti-angiogenic agents and anti-PD-1/PD-L1 antibodies had shown potent anti-tumor efficacy for unresectable or advanced hepatocellular carcinoma. However, the treatment options were limited when patients were failed the combination therapies. Hepatic artery infusion chemotherapy (HAIC) had shown potent anti-tumor efficacy with an acceptable safety profile as a first-line treatment for patients with intermediated-stage or advanced-stage hepatocellular carcinoma. In this study, the investigators aimed to evaluate the efficacy and safety of HAIC were used in the late-line setting, i.e., after the failure of combination therapy with anti-angiogenic agents and anti-PD-1/PD-L1 antibodies.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hepatocellular carcinoma diagnosed histologically/cytologically, or meeting the clinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition)."
- •Unresectable or advanced hepatocellular carcinoma that was assessed by the investigator. Advanced hepatocellular carcinoma was defined as BCLC C stage or Chinese Liver Cancer stage (CNLC) IIIa or IIIb stage.
- •Had at least one measurable lesion in the liver.
- •Liver function Child-Pugh classification of A or B
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patients who have received combination therapy with targeted agents combined with immune checkpoint inhibitors and have developed intolerable adverse effects or imaging confirmed intrahepatic tumor progression and have signed an informed consent form. Targeted agents include sorafenib, lenvatinib, donafenib, regorafenib, apatinib, bevacizumab (or biosimilar), and anlotinib; immune checkpoint inhibitors (mainly PD-1/PD-L1 antibodies) include pembrolizumab, nivolumab, camrelizumab, sintilimab, toripalimab, atezolizumab, and tislelizumab. Additional eligible subjects: subjects who have received at least one HAIC treatment were entered into safety evaluation (SAS); subjects who have received at least one imaging evaluation after treatment were entered into effectiveness evaluation (ITT).
- •Adequate bone marrow and organ function. Reassessment of bone marrow and organ function as described above is required prior to each HAIC treatment.
- •Leukocytes ≥ 3 x 10^9/L within the last 14 days.
- •Platelets ≥ 50×10^9/L in the last 14 days without transfusion.
- •hemoglobin ≥ 90 g/L in the last 14 days without blood transfusion or erythropoietin administration.
- •total bilirubin ≤ 2 x the upper limit of normal (ULN)
- •albumin ≥ 30 g/L in the absence of human albumin or plasma transfusion within the last 14 days
- •AST and ALT ≤ 3 x ULN.
- •serum creatinine at ≤1.5×ULN.
- •International Normalized Ratio (INR) of prothrombin time ≤ 1.5×ULN.
- •Serum HBV DNA < 2 x 10^3 IU/mL; for HBV DNA > 2 x 10^3 IU/mL, treatment with nucleoside analogs for at least 1 week.
- •Without grade 3 or higher adverse events (NCI CTCAE 4.0 criteria) induced by previous systemic therapy, or grade 3 or higher events reactions have recovered to grade 2 or lower.
排除标准
- •Pathologic diagnosed with mixed liver cancer, fibrous lamellar cell carcinoma or other non-hepatocellular malignancy component.
- •Previous or concurrent other malignancies, except adequately treated non-melanotic skin cancer, carcinoma in situ of the cervix, and papillary thyroid cancer
- •History of organ transplantation or hepatic encephalopathy.
- •Hypersensitivity to iodine-containing contrast agents, oxaliplatin, calcium folinic acid, and fluorouracil.
- •History of gastrointestinal perforation and/or fistula within 6 months, history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.
- •Uncontrollable hypertension, systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg after optimal medical therapy, history of hypertensive crisis or hypertensive encephalopathy.
- •Gastrointestinal bleeding due to portal hypertension within 6 months; G3 varices by gastrointestinal endoscopy within 3 months.
- •Subjects requesting withdrawal of informed consent.
- •Other circumstances that the investigator deems inappropriate for participation in the clinical trial.
研究组 & 干预措施
Hepatic Artery Infusion Chemotherapy
Subjects assigned to this arm will receive chemotherapy via catheterizations placed into the hepatic artery.
干预措施: Hepatic artery infusion chemotherapy with FOLFOX regimens (oxaliplatin, fluorouracil, and leucovorin) (Drug)
结局指标
主要结局
Objective response of intrahepatic lesions
时间窗: up to 1 year
Subjects with complete response or partial response assessed by RECIST v1.1 criteria.
次要结局
- The rate of adverse events(up to 1 year)
- duration of response of intrahepatic lesions(up to 1 year)
- Treatment cycles of HAIC(up to 1 year)
- Progression free survival(up to 1 year)
- Overall survival(up to 2 year)
- Ratio of R0 resection(up to 1 year)
研究者
Hui-Chuan Sun
Professor of Surgery
Shanghai Zhongshan Hospital