CS1008- in Combination With Sorafenib Compared to Sorafenib Alone in Subjects With Advanced Liver Cancer

NCT ID: NCT01033240

Last Updated: 2021-04-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

172 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-09

Study Completion Date

2013-09-09

Brief Summary

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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).

Detailed Description

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Conditions

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Advanced Hepatocellular Carcinoma Liver Cancer Hepatic Cancer Liver Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

CS-1008 2 mg/kg

Intervention Type DRUG

On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg.

Sorafenib

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

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.

CS-1008 4 mg/kg

Intervention Type DRUG

On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.

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.

Group Type ACTIVE_COMPARATOR

Sorafenib

Intervention Type DRUG

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.

CS-1008 6 mg/kg

Intervention Type DRUG

On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.

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)

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

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.

CS-1008 6/2 mg/kg

Intervention Type DRUG

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.

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)

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

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.

CS-1008 6/6 mg/kg

Intervention Type DRUG

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.

Treatment Group 3 with Sorafenib Alone

Sorafenib. Treatment Group 3: sorafenib twice daily (N=50)

Group Type EXPERIMENTAL

Sorafenib

Intervention Type DRUG

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.

Interventions

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CS-1008 2 mg/kg

On a once a week basis CS-1008 will be administered intravenously starting at 2 mg/kg.

Intervention Type DRUG

Sorafenib

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.

Intervention Type DRUG

CS-1008 6/2 mg/kg

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.

Intervention Type DRUG

CS-1008 6/6 mg/kg

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.

Intervention Type DRUG

CS-1008 4 mg/kg

On a once a week basis CS-1008 will be administered intravenously at 4 mg/kg if tolerated.

Intervention Type DRUG

CS-1008 6 mg/kg

On a once a week basis CS-1008 will be administered intravenously at 6 mg/kg if tolerated.

Intervention Type DRUG

Other Intervention Names

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Nexavar

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

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Kenmar Research Group

Los Angeles, California, United States

Site Status

Georgetown-Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Site Status

The Mount Sinai Medical Center

New York, New York, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Kurume University Hospital

Kurume-shi, Fukuoka, Japan

Site Status

Hiroshima University

Hiroshima, Hiroshima, Japan

Site Status

Kanazawa University

Kanazawa, Ishikawa-ken, Japan

Site Status

Kinki University Hospital

Osaka, Osaka-sayama, Japan

Site Status

Yamaguchi University Hospital

Ube, Yamaguchi, Japan

Site Status

Chiba University Hospital

Chiba, , Japan

Site Status

Okayama University Hospital

Okayama, , Japan

Site Status

Osaka Med Center Cancer and Cardiovascular Disease

Osaka, , Japan

Site Status

Musashino Red-Cross Hospital

Tokyo, , Japan

Site Status

Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Catholic Univ. of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Kaohiung Chang Gung Hospital

Kaohsiung City, Niaosung Hsiang, Taiwan

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Chang Gung Memorial Hospital

Chiayi City, , Taiwan

Site Status

Kaohslung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status

National Cheng-Kung University Hospital

Tainan City, , Taiwan

Site Status

Chi-Mei Medical Center

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation-Linkuo

Taoyuan District, , Taiwan

Site Status

Countries

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United States Japan South Korea Taiwan

References

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Cheng AL, Kang YK, He AR, Lim HY, Ryoo BY, Hung CH, Sheen IS, Izumi N, Austin T, Wang Q, Greenberg J, Shiratori S, Beckman RA, Kudo M; Investigators' Study Group. Safety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study. J Hepatol. 2015 Oct;63(4):896-904. doi: 10.1016/j.jhep.2015.06.001. Epub 2015 Jun 10.

Reference Type DERIVED
PMID: 26071796 (View on PubMed)

Other Identifiers

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CS1008-A-U204

Identifier Type: -

Identifier Source: org_study_id

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