A Phase II Study of Concurrent Nivolumab and External Beam Radiation Therapy for Patients With Advanced Hepatocellular Carcinoma Who Have Vascular Invasion With or Without Sorafenib-Experience in an HBV-endemic Area
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
To investigate the efficacy and safety of nivolumab for patients with advanced HCC undergoing EBRT
详细描述
<Treatment phase> Nivolumab 3mg/kg IV is administered as 30-minute IV infusion every 2 weeks. External beam radiotherapy begins 2-7 days after the first dose of nivolumab. The study drug is continued until disease progression, unacceptable toxicity, withdrawal of consent or study closure.
<Follow-Up phase > After the treatment phase, subjects will undergo follow up for survival every 12 weeks (± 7 days) from the last dose or the use of other anticancer treatments and/or therapies, and the survival follow up will be performed for at least 18 months after the enrollment of the last subject. The patient will be followed for survival follow up and the use of other anticancer treatments and/or therapies.
Based on the assumed dropout rate of 12%, a total of 50 subjects need to perform the study (50=44/(1-0.12))
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with HCC meeting all of following criteria;
- •Signed written informed consent
- •Histological or clinical diagnosis of HCC based on the guidelines of the Korean Liver Cancer Association-National Cancer Center17
- •Having at least one typical enhanced measurable index lesion (in the liver) by dynamic CT or dynamic contrast-enhanced MRI
- •Presence of major vascular invasion on dynamic CT or dynamic MRI
- •① an intraluminal filling defect adjacent to the primary tumor in portal vein, hepatic vein, and/or inferior vena cava
- •② an enhancement of the filling defect on arterial phase and a washout on portal/delayed phases.
- •Sorafenib naïve or sorafenib experienced
- •Child-Pugh class A
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
- •Life expectancy of at least 16 weeks
- •Adequate hematologic and hepatic function (should be obtained within 14 days prior to screening:
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1,000/mm3 ③ Platelet count ≥ 50,000/μL
- •Total bilirubin < 2.5 mg/dL
- •Serum albumin >2.8 g/dL ⑥ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × upper limit of normal (ULN) ⑦ Prothrombin time in INR ≤ 1.8 × ULN ⑧ Serum creatinine ≤ 1.5 mg/dL
- •Women of childbearing potential and men must agree to use highly efficient contraception since signing of the IC form until at least 5 months (women) and 7 months (men) after the last study drug administration.
排除标准
- •Patients with HCC meeting all of following criteria;
- •Receipt of 2 or more prior systemic therapies for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed.
- •Any type of anticancer agent (including investigational) within 2 weeks before enrollment
- •Having active brain metastasis or leptomeningeal metastasis
- •Moderate to severe or intractable ascites
- •A history or presence of hepatic encephalopathy
- •Presence of active bacterial infection
- •Untreated active chronic hepatitis B
- •History of portal hypertension with bleeding within the past 6 months
- •Prior liver transplant
- •Uncontrolled severe medical comorbidity
- •Other malignant disease (a history of treated malignancy -other than HCC- is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years)
- •Current or past history of hypersensitivity to nivolumab
研究组 & 干预措施
single
Nivolumab 3mg/kg IV is administered as 30-minute IV infusion every 2 weeks.
Prescription dose to PTVs as according to the following schema:
PTV1: 30 - 50 Gy /10 fx, 5Gy fraction dose, 5 days/week (The prescribed dose to PTV will be decided by physician depending on the dose-volume histogram (DVH) constraints of the normal tissues, such as liver, bowel, etc. The detail of DVH constraints of normal tissues are summarized in the following table) PTV2: 30 Gy /10 fx, 3Gy fraction dose, 5 days/week
干预措施: Nivolumab (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: through study completion, an average of 2.5 year.
Progression-free survival (PFS) is defined as the time from the date of treatment initiation to the date of the first observation of progressive disease (PD) by independent radiologic review according to RECIST criteria (version 1.1) or death from any cause.
次要结局
未报告次要终点
研究者
Joong-Won Park
Principal Investigator, Clinical Professor
National Cancer Center, Korea