Efficacy of Localized Concurrent Chemo-radiation Therapy and Sorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: a Prospective Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will receive CCRT and sorafenib sequentially until all-cause mortality.
详细描述
This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will receive CCRT and sorafenib sequentially until all-cause mortality.
Sorafenib is the current standard of care for advanced hepatocellular carcinoma (HCC) patients following clinical results from the two pivotal trials in Western and Asian patients. The median overall survival in patients with unresectable hepatocellular carcinoma (HCC) who are treated with sorafenib have shown to be approximately 14 months. However in the presence of portal vein invasion or extrahepatic metastases, the median overall survival is significantly lowered to 5.6 - 8.9 months.
Going forward, improvement in patient-related outcomes would be highly desirable.
A pilot study has been conducted in subjects with advanced HCC with portal vein invasion for which effective therapeutic methods have not been established. This was a single-center, open-label study of localized concurrent chemoradiation therapy (CCRT) for locally advanced HCC patients with portal vein invasion. A total of 40 subjects with advanced HCC with portal vein invasion were enrolled. The subjects were treated with a total of 45 Gy of external beam radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU 500 mg infusion for 5 hours) through the pre-inserted chemoport. Eighteen (45%) subjects had an objective tumor response at 1 month after completion of localized CCRT. The 3-year survival rate was 24.2% and median overall survival was 13.1 months.
Treatment-related serious adverse events (CTCAE grade 3 or higher) were anemia, leukopenia, thrombocytopenia, mucositis and liver decompensation, and their rates were 2.5%, 2.4-5.0%, 17.5%, 10% and 7.3-17.5%, respectively. In addition, 2.4-5.0% of adverse events were chemoport-related adverse events including infection and port obstruction.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have confirmed diagnosis of unresectable hepatocellular carcinoma (HCC) categorized to stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system with any of following criteria: 1) Lesion limited to a single lobe that is within the radiotherapy field, 2) Lesion not limited to a single lobe, but the lesion that is not within the radiotherapy field can be controlled by transarterial chemoembolization or radiofrequency ablation, 3) Presence of metastatic lesions that measure < 1.0 cm in the long axis, 4) The lesion can be accurately measured in at least one dimension as ≥ 1.0 cm
- •Males or females aged at least 20 years and below 76 years
- •Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 or 1
- •Adequate liver function, defined as: 1) Child-Pugh score ≤ 7, 2) Bilirubin ≤ 3.0 mg/dL
- •Adequate bone marrow function, defined as: 1) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, 2) White blood cell count (WBC) ≥ 4.0 × 109/L, 3) Platelet count ≥ 60 × 109/L
- •Adequate renal function, defined as serum creatinine < 2.0 mg/dL
- •Subjects with hepatitis B virus (HBV)-related HCC must have adequately controlled HBV replication status
- •Adequate blood coagulation factors, defined as international normalized ratio (INR) ≤ 2.3
- •Provide written informed consent
- •Willing and able to comply with all aspects of the protocol
排除标准
- •Significant liver function impairment, defined as bilirubin > 3.0 mg/dL or uncontrolled ascites
- •Imaging findings for HCC corresponding to any of the following: 1) Diffuse HCC with > 50% liver occupation, that is not adequate for external radiotherapy, 2) Presence of metastatic lesions that measure ≥ 1.0 cm in the long axis
- •Uncontrolled significant active infection
- •Presence of active malignancy (except for HCC)
- •Females who are lactating or pregnant; females of childbearing potential who have not received pregnancy test or shown positive on pregnancy test
- •Any medical or other condition that in the opinion of the investigator would preclude the subject's participation in a clinical study
- •Major surgery within 4 weeks prior to enrollment
研究组 & 干预措施
CCRT-sorafenib group
干预措施: CCRT (Radiation)
CCRT-sorafenib group
干预措施: sorafenib (Drug)
结局指标
主要结局
Overall survival
时间窗: 36 months after the enrollment
次要结局
- PFSL defined as dynamic CT scan(36 months after the enrollment)
- PFSO defined as definitive imaging technique(36 months after the enrollment)
- tumor response defined as modified RECIST(36 months after the enrollment)
- toxicity defined as NCI-CTC(version 4.02)(36 months after the enrollment)