CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer
2021년 4월 6일 업데이트: 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).
연구 개요
상태
완전한
정황
연구 유형
중재적
등록 (실제)
172
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Changhua, 대만, 500
- Changhua Christian Hospital
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Chiayi City, 대만
- Chang Gung Memorial Hospital
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Kaohsiung, 대만, 807
- Kaohslung Medical University Hospital
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Tainan, 대만, 73657
- Chi-Mei Medical Center
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Tainan city, 대만, 704
- National Cheng-Kung University Hospital
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Taipei, 대만
- National Taiwan University Hospital
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Taoyuan, 대만, 33305
- Chang Gung Medical Foundation-Linkuo
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Niaosung Hsiang
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Kaohsiung, Niaosung Hsiang, 대만
- Kaohiung Chang Gung Hospital
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Daegu, 대한민국, 700-712
- Keimyung University Dongsan Hospital
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Seoul, 대한민국, 135-710
- Samsung Medical Center
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Seoul, 대한민국, 138-736
- Asan Medical Center
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Seoul, 대한민국, 110-744
- Seoul National University Hospital
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Seoul, 대한민국, 120-752
- Severance Hospital
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Seoul, 대한민국, 136-705
- Korea University Anam Hospital
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Seoul, 대한민국, 137-701
- Catholic Univ. of Korea, Seoul St. Mary's Hospital
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California
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Los Angeles, California, 미국, 90057
- Kenmar Research Group
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District of Columbia
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Washington, District of Columbia, 미국, 20007
- Georgetown-Lombardi Cancer Center
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New York
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New York, New York, 미국, 10029
- The Mount Sinai Medical Center
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Tennessee
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Nashville, Tennessee, 미국, 37232
- Vanderbilt-Ingram Cancer Center
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Chiba, 일본, 260-8677
- Chiba University Hospital
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Okayama, 일본, 700-8558
- Okayama University Hospital
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Osaka, 일본, 537-8511
- Osaka Med Center Cancer and Cardiovascular Disease
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Tokyo, 일본, 180-8610
- Musashino Red-Cross Hospital
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Fukuoka
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Kurume-shi, Fukuoka, 일본, 830-0011
- Kurume University Hospital
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Hiroshima
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Hiroshima-city, Hiroshima, 일본
- Hiroshima University
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Ishikawa
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Kanazawa, Ishikawa, 일본
- Kanazawa University
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Osaka-sayama
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Osaka, Osaka-sayama, 일본, 589-8511
- Kinki University Hospital
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Yamaguchi
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Ube, Yamaguchi, 일본
- Yamaguchi University Hospital
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
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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.
다른 이름들:
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실험적: 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.
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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.
다른 이름들:
On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.
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활성 비교기: 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.
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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.
다른 이름들:
On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.
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실험적: 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.
다른 이름들:
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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실험적: 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)
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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.
다른 이름들:
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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실험적: 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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
기간: 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
기간: 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
기간: 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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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
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연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2010년 7월 9일
기본 완료 (실제)
2012년 7월 13일
연구 완료 (실제)
2013년 9월 9일
연구 등록 날짜
최초 제출
2009년 12월 15일
QC 기준을 충족하는 최초 제출
2009년 12월 15일
처음 게시됨 (추정)
2009년 12월 16일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2021년 4월 8일
QC 기준을 충족하는 마지막 업데이트 제출
2021년 4월 6일
마지막으로 확인됨
2021년 4월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- CS1008-A-U204
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
예
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
간 신생물에 대한 임상 시험
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University Hospital, Basel, Switzerland아직 모집하지 않음
CS-1008 2 mg/kg에 대한 임상 시험
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Ludwig Institute for Cancer ResearchDaiichi Sankyo, Inc.완전한
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Poitiers University Hospital완전한
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Instituto Nacional de Psiquiatría Dr. Ramón de...모병
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Hoag Memorial Hospital PresbyterianDa Zen Theranostics Inc초대로 등록
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Daiichi Sankyo, Inc.종료됨