NCT01774344已完成3 期
A Randomized, Double Blind, Placebo Controlled, Multicenter Phase III Study of Regorafenib in Patients With Hepatocellular Carcinoma (HCC) After Sorafenib
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 573
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The objective of this study was to evaluate efficacy and safety of regorafenib in patients with advanced liver cancer who had progressed after sorafenib treatment. Patients were treated with regorafenib or placebo using a 2:1 randomization scheme.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases criteria in patients with a confirmed diagnosis of cirrhosis
- •Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, local ablation, chemoembolization or systemic sorafenib.
- •Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last treatment with sorafenib.
- •Tolerability of prior treatment with sorafenib defined as not less than 20 days at a minimum daily dose of 400 mg QD within the last 28 days prior to withdrawal.
- •Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
- •Local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >/=4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intraarterial chemotherapy, without lipiodol or embolizing agents are not eligible.
- •Eastern Cooperative Oncology Group Performance Status of 0 or
- •Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 7 days before randomization.
- •Glomerular filtration rate >/= 30 ml/min/1.73 m^2 according to the Modification of diet in renal disease study equation.
- •At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST (RECIST version 1.1), and modified RECIST for HCC. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion.
- •Life expectancy of at least 3 months.
- •Women of childbearing potential and men must agree to use adequate contraception .
- •Exclusion Criteria :
- •Sorafenib treatment within 2 weeks of randomization.
- •Prior systemic treatment for HCC, except sorafenib.
- •Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
- •Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease).
- •Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
- •Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
- •Ongoing infection > Grade 2 according to NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v. 4.
- •Hepatitis B is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required.
- •Clinically significant bleeding NCI-CTCAE version 4.0 Grade 3 or higher within 30 days before randomization.
- •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication.
- •Patients unable to swallow oral medications.
- •Interstitial lung disease with ongoing signs and symptoms at the time of screening.
排除标准
- 未提供
研究组 & 干预措施
Regorafenib
Experimental
160 mg orally (p.o.) every day (qd) for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC (Best Supportive Care)
干预措施: Regorafenib (Stivarga, BAY73-4506) (Drug)
Placebo
Placebo Comparator
4 matching placebo tablets for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization (Day 1) of the first subject until 419 days later
Overall Survival (OS) was defined as the time from date of randomization (Day 1) to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
次要结局
- Time to Progression (TTP)(From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months))
- Progression Free Survival (PFS)(From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks))
- Objective Tumor Response Rate (ORR)(From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months))
- Disease Control Rate (DCR)(From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months))
研究者
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