CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer
2021年4月6日 更新者：Daiichi Sankyo, Inc.
Clinical Study Protocol Phase 2, Randomized Study of CS-1008 in Combination With Sorafenib Compared to Sorafenib Alone as First-Line Systemic Therapy in Subjects With Advanced Hepatocellular Carcinoma
The purpose of this study is to determine the safety and efficacy of CS-1008 in combination with sorafenib to sorafenib alone for treating liver cancer.
Approximately 160 participants will take part in this study at approximately 22 sites (4 in the US, 8 in Japan, and 10 in Asia).
研究概览
地位
完全的
研究类型
介入性
注册 (实际的)
172
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Changhua、台湾、500
- Changhua Christian Hospital
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Chiayi City、台湾
- Chang Gung Memorial Hospital
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Kaohsiung、台湾、807
- Kaohslung Medical University Hospital
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Tainan、台湾、73657
- Chi-Mei Medical Center
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Tainan city、台湾、704
- National Cheng-Kung University Hospital
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Taipei、台湾
- National Taiwan University Hospital
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Taoyuan、台湾、33305
- Chang Gung Medical Foundation-Linkuo
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Niaosung Hsiang
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Kaohsiung、Niaosung Hsiang、台湾
- Kaohiung Chang Gung Hospital
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Daegu、大韩民国、700-712
- Keimyung University Dongsan Hospital
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Seoul、大韩民国、135-710
- Samsung Medical Center
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Seoul、大韩民国、138-736
- Asan Medical Center
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Seoul、大韩民国、110-744
- Seoul National University Hospital
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Seoul、大韩民国、120-752
- Severance Hospital
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Seoul、大韩民国、136-705
- Korea University Anam Hospital
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Seoul、大韩民国、137-701
- Catholic Univ. of Korea, Seoul St. Mary's Hospital
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Chiba、日本、260-8677
- Chiba University Hospital
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Okayama、日本、700-8558
- Okayama University Hospital
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Osaka、日本、537-8511
- Osaka Med Center Cancer and Cardiovascular Disease
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Tokyo、日本、180-8610
- Musashino Red-Cross Hospital
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Fukuoka
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Kurume-shi、Fukuoka、日本、830-0011
- Kurume University Hospital
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Hiroshima
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Hiroshima-city、Hiroshima、日本
- Hiroshima University
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Ishikawa
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Kanazawa、Ishikawa、日本
- Kanazawa University
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Osaka-sayama
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Osaka、Osaka-sayama、日本、589-8511
- Kinki University Hospital
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Yamaguchi
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Ube、Yamaguchi、日本
- Yamaguchi University Hospital
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California
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Los Angeles、California、美国、90057
- Kenmar Research Group
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District of Columbia
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Washington、District of Columbia、美国、20007
- Georgetown-Lombardi Cancer Center
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New York
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New York、New York、美国、10029
- The Mount Sinai Medical Center
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Tennessee
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Nashville、Tennessee、美国、37232
- Vanderbilt-Ingram Cancer Center
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or clinical diagnosis of HCC when the following criteria are all met:
- History of chronic hepatitis and/or cirrhosis of liver;
- Typical features of HCC demonstrated in dynamic imaging studies, such as three-phase computed tomography (CT); AND
- Alpha-fetoprotein (AFP) level > 200 ng/mL
Advanced diseases
- Extrahepatic metastasis, OR
- Locally advanced diseases which are not amenable for surgical resection or other loco-regional therapies including transhepatic arterial (chemo) embolization (TACE or TAE) and local ablative therapy
- Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of at least 1 untreated target lesion that can be measured in 1 dimension
- At least 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Child-Pugh class A
- Life expectancy of at least 12 weeks
Adequate organ and bone marrow function as assessed by clinical laboratory evaluations:
- Hemoglobin ≥ 8.5 g/dL (transfusion and/or growth factor support allowed)
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
- Platelet count ≥ 75 x 10^9/L
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance > 40 mL/min
- Aspartate Aminotransferase (AST) and alkaline phosphatase ≤ 5.0 x ULN
- Total bilirubin ≤ 1.5 x ULN
- Serum amylase and lipase ≤ 1.5 x ULN
- Women of childbearing potential must be willing to consent to using effective contraception (eg, abstinence, hormonal contraceptives, bilateral tubal ligation, barrier with spermicide, intrauterine device) while on treatment and for 3 months thereafter. Men who are the partner of a woman of childbearing potential must be willing to consent to using effective contraception (eg, vasectomy or barrier with spermicide) while on treatment and for 3 months thereafter
- All female participants of childbearing potential must have a negative pregnancy test (serum or urine) result
- Participants must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an International Review Board (IRB)/ Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before the performance of any study specific procedures or tests
- Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion Criteria:
- Any prior systemic therapy for HCC, including systemic chemotherapy (prior exposure to chemotherapy by TACE is allowed), immunotherapy, sorafenib or other Raf kinase inhibitors, Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR)-inhibitors, epidermal growth factor receptor inhibitors or mechanistic target of rapamycin (mTOR) inhibitors
- Radiotherapy or major surgical procedure within 4 weeks of the screening/baseline visit or minor surgical procedures (eg, core biopsy or fine needle aspiration) within 2 weeks of the screening/baseline visit
- Anticipation of need for radiotherapy (RT) or a major surgical procedure during the study
- Any investigational agent within 4 weeks before the screening/baseline visit
History of any of the following conditions within 6 months before the screening/baseline visit:
- Myocardial infarction with significant impairment of cardiac function (eg, ejection fraction ≤ 30%)
- Severe/unstable angina pectoris
- New York Heart Association (NYHA) class III or intravenous (IV) congestive heart failure
- Clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma)
- Clinically active brain metastases (defined as untreated, symptomatic or requiring steroids or anticonvulsants medications to control associated symptoms), uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis. Participants with treated brain metastasis will be included in the study if they have recovered from the acute, toxic effects of radiotherapy. A minimum of 15 days must have elapsed between the end of RT and the screening/baseline visit
- History of organ transplantation
- Clinically significant, severe, active infection requiring IV antibiotics
- Known history of human immunodeficiency virus (HIV) infection
- History of prior sensitivity reaction to any components of CS-1008 or sorafenib formulations
- History of a second malignancy, with the exception of in situ cervical cancer or adequately treated basal cell or squamous cell carcinoma of the skin
- Pregnant or breast feeding
- Serious intercurrent medical illnesses that, in the opinion of the Investigator, would impair the participant's ability to provide informed consent or unacceptably reduce the safety of the proposed treatment
- Clinically significant (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] grade ≥ 3) gastrointestinal bleeding in the past 12 months or current active gastrointestinal bleeding
- Presence of esophageal varices at risk of bleeding, such as large esophageal/gastric varices or those with red sign, or active peptic ulcer with or without exposed vessels at risk of bleeding (as documented by endoscopy)
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 6 months
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Safety Cohort 1 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (2 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
|
On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg.
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
其他名称：
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实验性的：Safety Cohort 2 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (4 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
|
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
其他名称：
On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.
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有源比较器：Safety Cohort 3 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib; CS-1008 (6 mg/kg per week) in combination with sorafenib (400 mg self-administered by mouth twice daily) over 4 weeks observation, and may continue treatment until progression.
|
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
其他名称：
On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.
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实验性的：Treatment Group 1 CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib.
Treatment Group 1: CS-1008 (6 mg/kg [or as determined] loading, 2 mg/kg/week maintenance) + sorafenib twice daily (N=50)
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
其他名称：
A 6 mg/kg loading dose of CS-1008 will be administered intravenously, followed by a 2 mg/kg/week maintenance dose on a once-a-week basis.
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实验性的：Treatment Group 2 with CS-1008 and Sorafenib
Combination of CS-1008 and sorafenib.
Treatment Group 2: CS-1008 (6 mg/kg [or as determined] loading, 6 mg/kg/week [or maximum tolerated dose {MTD}] maintenance) + sorafenib twice daily (N=50)
|
On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
其他名称：
A 6 mg/kg loading dose of CS-1008 will be administered intravenously, followed by a 6 mg/kg/week maintenance dose on a once-a-week basis.
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实验性的：Treatment Group 3 with Sorafenib Alone
Sorafenib.
Treatment Group 3: sorafenib twice daily (N=50)
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On a daily basis, one sorafenib tablet, 400 mg, is taken orally twice a day.
The total daily dose of sorafenib is 800 mg.
The sorafenib tablets are taken at least 1 hour before or 2 hours after a meal.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
大体时间：Baseline up to approximately 2 years post-dose.
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Time to progression was defined as the time from randomization to the date of the first objective documentation of radiographic or symptomatic progression, whichever came first.
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Baseline up to approximately 2 years post-dose.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
大体时间：Baseline up to approximately 3 years 2 months post-dose.
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Overall survival (OS) was defined as the time from randomization to the date of death.
The factors in the final model were treatment, Eastern Cooperative Oncology Group (ECOG) performance status, presence of extrahepatic metastasis and/or macrovessel invasion, and region.
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Baseline up to approximately 3 years 2 months post-dose.
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Best Overall Response and Objective Response Rate Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
大体时间：Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 3 years 2 months post-dose.
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The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdraws from the study based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
If there is no tumor assessment after the first dose of study drug, the best overall response is classified as Inevaluable.
CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.
Objective response rate was defined as confirmed CR and confirmed PR.
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Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 3 years 2 months post-dose.
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Treatment-Emergent Adverse Events Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
大体时间：Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.
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Treatment-Emergent Adverse Events (TEAEs) were defined as those adverse events (AEs) that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration.
An AE that occurred more than 30 days after the last dose of study medication was not included as a TEAE unless it was considered related to treatment or the assessment of relatedness was missing.
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Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2010年7月9日
初级完成 (实际的)
2012年7月13日
研究完成 (实际的)
2013年9月9日
研究注册日期
首次提交
2009年12月15日
首先提交符合 QC 标准的
2009年12月15日
首次发布 (估计)
2009年12月16日
研究记录更新
最后更新发布 (实际的)
2021年4月8日
上次提交的符合 QC 标准的更新
2021年4月6日
最后验证
2021年4月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.