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).
調査の概要
状態
完了
研究の種類
介入
入学 (実際)
172
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Los Angeles、California、アメリカ、90057
- Kenmar Research Group
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District of Columbia
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Washington、District of Columbia、アメリカ、20007
- Georgetown-Lombardi Cancer Center
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New York
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New York、New York、アメリカ、10029
- The Mount Sinai Medical Center
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Tennessee
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Nashville、Tennessee、アメリカ、37232
- Vanderbilt-Ingram Cancer Center
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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、大韓民国、700-712
- Keimyung University Dongsan Hospital
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Seoul、大韓民国、135-710
- Samsung Medical Center
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Seoul、大韓民国、138-736
- Asan Medical Center
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Seoul、大韓民国、110-744
- Seoul National University Hospital
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Seoul、大韓民国、120-752
- Severance Hospital
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Seoul、大韓民国、136-705
- Korea University Anam Hospital
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Seoul、大韓民国、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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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
他の名前：
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実験的：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.
他の名前：
On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.
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アクティブコンパレータ：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.
他の名前：
On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.
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実験的：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)
|
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.
他の名前：
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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実験的：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.
他の名前：
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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実験的：Treatment Group 3 with Sorafenib Alone
Sorafenib.
Treatment Group 3: 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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
時間枠：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
時間枠：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
時間枠：Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.
|
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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スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2010年7月9日
一次修了 (実際)
2012年7月13日
研究の完了 (実際)
2013年9月9日
試験登録日
最初に提出
2009年12月15日
QC基準を満たした最初の提出物
2009年12月15日
最初の投稿 (見積もり)
2009年12月16日
学習記録の更新
投稿された最後の更新 (実際)
2021年4月8日
QC基準を満たした最後の更新が送信されました
2021年4月6日
最終確認日
2021年4月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。