Clincosm LogoSign in Get a demo

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

Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01033240
Collaborator
(none)
172
Enrollment
28
Locations
6
Arms
38
Actual Duration (Months)
6.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
  • Drug: CS-1008 2 mg/kg
  • Drug: Sorafenib
  • Drug: CS-1008 6/2 mg/kg
  • Drug: CS-1008 6/6 mg/kg
  • Drug: CS-1008 4 mg/kg
  • Drug: CS-1008 6 mg/kg
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
172 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jul 9, 2010
Actual Primary Completion Date :
Jul 13, 2012
Actual Study Completion Date :
Sep 9, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

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

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.
Other Names:
  • Nexavar

    		•
    Experimental: 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.

    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.
    Other Names:
  • Nexavar

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

    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.
    Other Names:
  • Nexavar

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

    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.
    Other Names:
  • Nexavar

    • 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.
    Experimental: 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)

    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.
    Other Names:
  • Nexavar

    • 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.
    Experimental: Treatment Group 3 with Sorafenib Alone

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

    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.
    Other Names:
  • Nexavar

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer [Baseline up to approximately 2 years post-dose.]

      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.

    Secondary Outcome Measures

    1. Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer [Baseline up to approximately 3 years 2 months post-dose.]

      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.

    2. Best Overall Response and Objective Response Rate Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer [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.]

      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.

    3. Treatment-Emergent Adverse Events Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kenmar Research Group Los Angeles California United States 90057
    2 Georgetown-Lombardi Cancer Center Washington District of Columbia United States 20007
    3 The Mount Sinai Medical Center New York New York United States 10029
    4 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232
    5 Kurume University Hospital Kurume-shi Fukuoka Japan 830-0011
    6 Hiroshima University Hiroshima-city Hiroshima Japan
    7 Kanazawa University Kanazawa Ishikawa Japan
    8 Kinki University Hospital Osaka Osaka-sayama Japan 589-8511
    9 Yamaguchi University Hospital Ube Yamaguchi Japan
    10 Chiba University Hospital Chiba Japan 260-8677
    11 Okayama University Hospital Okayama Japan 700-8558
    12 Osaka Med Center Cancer and Cardiovascular Disease Osaka Japan 537-8511
    13 Musashino Red-Cross Hospital Tokyo Japan 180-8610
    14 Keimyung University Dongsan Hospital Daegu Korea, Republic of 700-712
    15 Seoul National University Hospital Seoul Korea, Republic of 110-744
    16 Severance Hospital Seoul Korea, Republic of 120-752
    17 Samsung Medical Center Seoul Korea, Republic of 135-710
    18 Korea University Anam Hospital Seoul Korea, Republic of 136-705
    19 Catholic Univ. of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 137-701
    20 Asan Medical Center Seoul Korea, Republic of 138-736
    21 Kaohiung Chang Gung Hospital Kaohsiung Niaosung Hsiang Taiwan
    22 Changhua Christian Hospital Changhua Taiwan 500
    23 Chang Gung Memorial Hospital Chiayi City Taiwan
    24 Kaohslung Medical University Hospital Kaohsiung Taiwan 807
    25 National Cheng-Kung University Hospital Tainan city Taiwan 704
    26 Chi-Mei Medical Center Tainan Taiwan 73657
    27 National Taiwan University Hospital Taipei Taiwan
    28 Chang Gung Medical Foundation-Linkuo Taoyuan Taiwan 33305

    Sponsors and Collaborators

    • Daiichi Sankyo, Inc.

    Investigators

    • Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Daiichi Sankyo, Inc.
    ClinicalTrials.gov Identifier:
    NCT01033240
    Other Study ID Numbers:
    • CS1008-A-U204
    First Posted:
    Dec 16, 2009
    Last Update Posted:
    Apr 8, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Daiichi Sankyo, Inc.
    Sorafenib
    CS-1008
    Advanced Liver Cancer
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Liver Neoplasms
    Sorafenib

    Study Results

    Participant Flow

    Recruitment Details A total of 172 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at clinic sites in the United States of America (USA), Japan, Taiwan, and South Korea. Ten (10) of the participants were enrolled but did not receive treatment. The data on the 162 treated participants are presented in this report.
    Pre-assignment Detail
    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles.
    Period Title: Overall Study
    STARTED 55 53 55
    COMPLETED 6 3 2
    NOT COMPLETED 49 50 53

    Baseline Characteristics

    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib Total
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Total of all reporting groups
    Overall Participants 55 53 54 162
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.2
    (11.36)
    60.7
    (12.92)
    61.1
    (12.47)
    62.4
    (12.35)
    Sex: Female, Male (Count of Participants)
    Female
    11
    20%
    8
    15.1%
    9
    16.7%
    28
    17.3%
    Male
    44
    80%
    45
    84.9%
    45
    83.3%
    134
    82.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    34
    61.8%
    32
    60.4%
    37
    68.5%
    103
    63.6%
    Unknown or Not Reported
    21
    38.2%
    21
    39.6%
    17
    31.5%
    59
    36.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    54
    98.2%
    52
    98.1%
    53
    98.1%
    159
    98.1%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    1.8%
    0
    0%
    1
    1.9%
    2
    1.2%
    White
    0
    0%
    1
    1.9%
    0
    0%
    1
    0.6%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    South Korea
    20
    36.4%
    15
    28.3%
    18
    33.3%
    53
    32.7%
    United States
    1
    1.8%
    1
    1.9%
    1
    1.9%
    3
    1.9%
    Japan
    17
    30.9%
    17
    32.1%
    18
    33.3%
    52
    32.1%
    Taiwan
    17
    30.9%
    20
    37.7%
    17
    31.5%
    54
    33.3%

    Outcome Measures

    1. Primary Outcome
    Title Time to Progression (TTP) Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
    Description 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.
    Time Frame Baseline up to approximately 2 years post-dose.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set was used to assess TTP.
    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles.
    Measure Participants 55 53 54
    Median (95% Confidence Interval) [months]
    2.8
    3.0
    3.9
    2. Secondary Outcome
    Title Overall Survival Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
    Description 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.
    Time Frame Baseline up to approximately 3 years 2 months post-dose.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set was used to assess overall survival.
    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles.
    Measure Participants 55 53 54
    Median (95% Confidence Interval) [months]
    8.2
    8.2
    12.2
    3. Secondary Outcome
    Title Best Overall Response and Objective Response Rate Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
    Description 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.
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    The full analysis set was used to assess the best overall response and objective response rate.
    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles.
    Measure Participants 55 53 54
    Complete Response (CR)
    0
    0%
    0
    0%
    0
    0%
    Partial Response (PR)
    6
    10.9%
    3
    5.7%
    8
    14.8%
    Objective Response Rate (CR+PR)
    6
    10.9%
    3
    5.7%
    8
    14.8%
    Stable Disease (SD)
    24
    43.6%
    26
    49.1%
    29
    53.7%
    Progressive Disease (PD)
    20
    36.4%
    14
    26.4%
    15
    27.8%
    Inevaluable
    5
    9.1%
    10
    18.9%
    2
    3.7%
    Best Overall Response of SD or Better
    30
    54.5%
    29
    54.7%
    37
    68.5%
    4. Secondary Outcome
    Title Treatment-Emergent Adverse Events Following CS1008 in Combination With Sorafenib Compared to Sorafenib Alone in Participants With Advanced Liver Cancer
    Description 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.
    Time Frame Baseline up to 30 days after last dose, up to approximately 3 years 2 months post-dose.

    Outcome Measure Data

    Analysis Population Description
    Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.
    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles.
    Measure Participants 55 52 55
    Subjects with ≥1 TEAE
    54
    98.2%
    52
    98.1%
    54
    100%
    TEAEs by worst CTCAE grade: CTCAE grade: Grade ≥ 3
    43
    78.2%
    44
    83%
    46
    85.2%
    TEAEs by worst CTCAE grade: Grade 5
    10
    18.2%
    8
    15.1%
    5
    9.3%
    TEAEs related to CS-1008
    NA
    NaN
    40
    75.5%
    39
    72.2%
    TEAEs related to sorafenib
    53
    96.4%
    51
    96.2%
    54
    100%
    Discontinued CS-1008 due to TEAE
    0
    0%
    5
    9.4%
    8
    14.8%
    Discontinued sorafenib due to TEAE
    18
    32.7%
    7
    13.2%
    9
    16.7%
    Treatment-Emergent SAEs
    25
    45.5%
    26
    49.1%
    20
    37%
    TEAEs leading to death
    11
    20%
    8
    15.1%
    6
    11.1%
    Deaths
    34
    61.8%
    31
    58.5%
    29
    53.7%

    Adverse Events

    Time Frame Treatment-emergent adverse events (TEAEs) data were collected from Baseline up to 30 days after the last dose, up to approximately 3 years 2 months post-dose.
    Adverse Event Reporting Description 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 that occurred >30 days after 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.
    Arm/Group Title Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Arm/Group Description Participants with advanced hepatocellular carcinoma who were administered sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 2 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles. Participants with advanced hepatocellular carcinoma who were administered a combination of CS-1008 (6 mg/kg loading dose followed by 6 mg/kg/week maintenance dose) intravenously (IV) once a week + sorafenib (400 mg) orally twice daily over 3-week treatment cycles.
    All Cause Mortality
    Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 34/55 (61.8%) 31/52 (59.6%) 29/55 (52.7%)
    Serious Adverse Events
    Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/55 (45.5%) 26/52 (50%) 20/55 (36.4%)
    Blood and lymphatic system disorders
    Anaemia 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Pancytopenia 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Thrombocytopenia 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Cardiac disorders
    Atrial fibrillation 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Sinus arrest 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Abdominal pain 0/55 (0%) 1/52 (1.9%) 1/55 (1.8%)
    Abdominal pain upper 0/55 (0%) 1/52 (1.9%) 1/55 (1.8%)
    Ascites 1/55 (1.8%) 5/52 (9.6%) 0/55 (0%)
    Diarrhoea 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Duodenal ulcer haemorrhage 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Gastric varices haemorrhage 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Gastritis 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Gingival bleeding 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Haematochezia 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Haemorrhoids 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Oesophageal varices haemorrhage 1/55 (1.8%) 1/52 (1.9%) 1/55 (1.8%)
    Pancreatitis acute 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Stomatitis 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Upper gastrointestinal haemorrhage 2/55 (3.6%) 1/52 (1.9%) 0/55 (0%)
    Varices oesophageal 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    General disorders
    Asthenia 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Disease progression 6/55 (10.9%) 6/52 (11.5%) 5/55 (9.1%)
    Fatigue 1/55 (1.8%) 1/52 (1.9%) 0/55 (0%)
    Multi-organ failure 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Oedema peripheral 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Pyrexia 1/55 (1.8%) 2/52 (3.8%) 1/55 (1.8%)
    Hepatobiliary disorders
    Bile duct obstruction 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Cholangitis 1/55 (1.8%) 0/52 (0%) 1/55 (1.8%)
    Hepatic cirrhosis 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Hepatic failure 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Hepatic function abnormal 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Hepatic infarction 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Hyperbilirubinaemia 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Jaundice cholestatic 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Infections and infestations
    Appendicitis 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Biliary sepsis 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Peritonitis bacterial 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Pneumonia 1/55 (1.8%) 1/52 (1.9%) 1/55 (1.8%)
    Sepsis 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Urinary tract infection 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Injury, poisoning and procedural complications
    Fall 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Spinal compression fracture 0/55 (0%) 0/52 (0%) 0/55 (0%)
    Investigations
    Blood amylase increased 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    C-reactive protein increased 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Metabolism and nutrition disorders
    Decreased appetitie 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Dehydration 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Hyperkalaemia 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Hypoglycaemia 1/55 (1.8%) 0/52 (0%) 1/55 (1.8%)
    Tumour lysis syndrome 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Bone pain 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Flank pain 0/55 (0%) 0/52 (0%) 0/55 (0%)
    Myositis 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Rhabdomyolysis 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Large intestine carcinoma 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Metastases to bone 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Neoplasm progression 0/55 (0%) 0/52 (0%) 0/55 (0%)
    Tumour necrosis 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Tumour pain 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Nervous system disorders
    Altered state of consciousness 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Cerebrovascular accident 0/55 (0%) 0/52 (0%) 0/55 (0%)
    Hepatic encephalopathy 4/55 (7.3%) 1/52 (1.9%) 1/55 (1.8%)
    Psychiatric disorders
    Delirium 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Renal and urinary disorders
    Azotaemia 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Renal failure acute 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Urethral stenosis 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Respiratory, thoracic and mediastinal disorders
    Hiccups 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Pleural effusion 1/55 (1.8%) 2/52 (3.8%) 0/55 (0%)
    Skin and subcutaneous tissue disorders
    Drug eruption 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Erythema multiforme 1/55 (1.8%) 0/52 (0%) 0/55 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Rash maculo-papular 0/55 (0%) 0/52 (0%) 1/55 (1.8%)
    Vascular disorders
    Haemorrhage 0/55 (0%) 1/52 (1.9%) 0/55 (0%)
    Other (Not Including Serious) Adverse Events
    Sorafenib CS-1008 6/2 mg/kg + Sorafenib CS-1008 6/6 mg/kg + Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 54/55 (98.2%) 52/52 (100%) 54/55 (98.2%)
    Blood and lymphatic system disorders
    Anaemia 6/55 (10.9%) 5/52 (9.6%) 7/55 (12.7%)
    Leukopenia 0/55 (0%) 2/52 (3.8%) 3/55 (5.5%)
    Thrombocytopenia 2/55 (3.6%) 5/52 (9.6%) 6/55 (10.9%)
    Ear and labyrinth disorders
    Tinnitus 4/55 (7.3%) 1/52 (1.9%) 3/55 (5.5%)
    Gastrointestinal disorders
    Abdominal discomfort 4/55 (7.3%) 4/52 (7.7%) 1/55 (1.8%)
    Abdominal distension 10/55 (18.2%) 8/52 (15.4%) 5/55 (9.1%)
    Abdominal pain 12/55 (21.8%) 14/52 (26.9%) 17/55 (30.9%)
    Abdominal pain upper 3/55 (5.5%) 10/52 (19.2%) 13/55 (23.6%)
    Ascites 14/55 (25.5%) 14/52 (26.9%) 7/55 (12.7%)
    Cheilitis 0/55 (0%) 1/52 (1.9%) 3/55 (5.5%)
    Constipation 9/55 (16.4%) 19/52 (36.5%) 13/55 (23.6%)
    Diarrhoea 27/55 (49.1%) 23/52 (44.2%) 36/55 (65.5%)
    Dry Mouth 5/55 (9.1%) 1/52 (1.9%) 1/55 (1.8%)
    Dyspepsia 1/55 (1.8%) 2/52 (3.8%) 7/55 (12.7%)
    Gingival bleeding 3/55 (5.5%) 3/52 (5.8%) 1/55 (1.8%)
    Mouth ulceration 3/55 (5.5%) 0/52 (0%) 1/55 (1.8%)
    Nausea 8/55 (14.5%) 10/52 (19.2%) 11/55 (20%)
    Stomatitis 6/55 (10.9%) 5/52 (9.6%) 6/55 (10.9%)
    Vomiting 7/55 (12.7%) 5/52 (9.6%) 10/55 (18.2%)
    General disorders
    Asthenia 5/55 (9.1%) 6/52 (11.5%) 3/55 (5.5%)
    Chills 3/55 (5.5%) 5/52 (9.6%) 4/55 (7.3%)
    Disease progression 6/55 (10.9%) 6/52 (11.5%) 5/55 (9.1%)
    Fatigue 17/55 (30.9%) 13/52 (25%) 14/55 (25.5%)
    Malaise 6/55 (10.9%) 6/52 (11.5%) 7/55 (12.7%)
    Oedema peripheral 11/55 (20%) 14/52 (26.9%) 10/55 (18.2%)
    Pyrexia 9/55 (16.4%) 16/52 (30.8%) 15/55 (27.3%)
    Hepatobiliary disorders
    Hepatic function abnormal 2/55 (3.6%) 0/52 (0%) 3/55 (5.5%)
    Hyperbilirubinaemia 4/55 (7.3%) 1/52 (1.9%) 2/55 (3.6%)
    Infections and infestations
    Nasopharyngitis 2/55 (3.6%) 2/52 (3.8%) 5/55 (9.1%)
    Pneumonia 3/55 (5.5%) 1/52 (1.9%) 1/55 (1.8%)
    Upper respiratory tract infection 1/55 (1.8%) 8/52 (15.4%) 5/55 (9.1%)
    Investigations
    Alanine aminotransferase increased 14/55 (25.5%) 14/52 (26.9%) 15/55 (27.3%)
    Aspartate aminotransferase increased 24/55 (43.6%) 20/52 (38.5%) 21/55 (38.2%)
    Blood alkaline phosphatase increased 5/55 (9.1%) 3/52 (5.8%) 9/55 (16.4%)
    Blood amylase increased 8/55 (14.5%) 12/52 (23.1%) 11/55 (20%)
    Blood bilirubin increased 13/55 (23.6%) 12/52 (23.1%) 9/55 (16.4%)
    Blood creatine phosphokinase increased 4/55 (7.3%) 2/52 (3.8%) 7/55 (12.7%)
    Blood creatinine increased 4/55 (7.3%) 3/52 (5.8%) 1/55 (1.8%)
    Blood lactate dehydrogenase increased 6/55 (10.9%) 5/52 (9.6%) 7/55 (12.7%)
    Blood urea increased 3/55 (5.5%) 3/52 (5.8%) 1/55 (1.8%)
    Lipase increased 19/55 (34.5%) 17/52 (32.7%) 17/55 (30.9%)
    Lymphocyte count decreased 4/55 (7.3%) 8/52 (15.4%) 10/55 (18.2%)
    Neutrophil count decreased 4/55 (7.3%) 1/52 (1.9%) 3/55 (5.5%)
    Platelet count decreased 14/55 (25.5%) 8/52 (15.4%) 15/55 (27.3%)
    Weight blood cell count decreased 4/55 (7.3%) 5/52 (9.6%) 3/55 (5.5%)
    Metabolism and nutrition disorders
    Decreased appetite 25/55 (45.5%) 25/52 (48.1%) 26/55 (47.3%)
    Hyperglycaemia 0/55 (0%) 5/52 (9.6%) 3/55 (5.5%)
    Hyperkalaemia 2/55 (3.6%) 3/52 (5.8%) 2/55 (3.6%)
    Hypoalbuminaemia 13/55 (23.6%) 12/52 (23.1%) 12/55 (21.8%)
    Hypocalcaemia 3/55 (5.5%) 2/52 (3.8%) 4/55 (7.3%)
    Hypoglycaemia 2/55 (3.6%) 0/52 (0%) 3/55 (5.5%)
    Hypokalaemia 4/55 (7.3%) 2/52 (3.8%) 3/55 (5.5%)
    Hyponatraemia 7/55 (12.7%) 3/52 (5.8%) 3/55 (5.5%)
    Hypophosphataemia 14/55 (25.5%) 17/52 (32.7%) 17/55 (30.9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/55 (9.1%) 2/52 (3.8%) 1/55 (1.8%)
    Back pain 8/55 (14.5%) 7/52 (13.5%) 11/55 (20%)
    Flank pain 3/55 (5.5%) 2/52 (3.8%) 0/55 (0%)
    Musculoskeletal chest pain 1/55 (1.8%) 2/52 (3.8%) 4/55 (7.3%)
    Musculoskeletal pain 3/55 (5.5%) 7/52 (13.5%) 6/55 (10.9%)
    Myalgia 1/55 (1.8%) 1/52 (1.9%) 3/55 (5.5%)
    Neck pain 3/55 (5.5%) 0/52 (0%) 1/55 (1.8%)
    Pain in extremity 5/55 (9.1%) 4/52 (7.7%) 2/55 (3.6%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 1/55 (1.8%) 2/52 (3.8%) 3/55 (5.5%)
    Nervous system disorders
    Dizziness 5/55 (9.1%) 4/52 (7.7%) 2/55 (3.6%)
    Dysgeusia 3/55 (5.5%) 1/52 (1.9%) 2/55 (3.6%)
    Headache 4/55 (7.3%) 8/52 (15.4%) 9/55 (16.4%)
    Hepatic encephalopathy 4/55 (7.3%) 1/52 (1.9%) 1/55 (1.8%)
    Neuropathy peripheral 0/55 (0%) 1/52 (1.9%) 3/55 (5.5%)
    Psychiatric disorders
    Insomnia 5/55 (9.1%) 8/52 (15.4%) 11/55 (20%)
    Renal and urinary disorders
    Proteinuria 2/55 (3.6%) 2/52 (3.8%) 3/55 (5.5%)
    Respiratory, thoracic and mediastinal disorders
    Cough 7/55 (12.7%) 7/52 (13.5%) 11/55 (20%)
    Dysphonia 14/55 (25.5%) 14/52 (26.9%) 14/55 (25.5%)
    Dyspnoea 5/55 (9.1%) 3/52 (5.8%) 2/55 (3.6%)
    Dyspnoea exertional 0/55 (0%) 0/52 (0%) 3/55 (5.5%)
    Epistaxis 2/55 (3.6%) 3/52 (5.8%) 5/55 (9.1%)
    Haemoptysis 3/55 (5.5%) 1/52 (1.9%) 2/55 (3.6%)
    Oropharyngeal pain 3/55 (5.5%) 4/52 (7.7%) 3/55 (5.5%)
    Pleural effusion 3/55 (5.5%) 3/52 (5.8%) 0/55 (0%)
    Productive cough 5/55 (9.1%) 1/52 (1.9%) 0/55 (0%)
    Skin and subcutaneous tissue disorders
    Acne 3/55 (5.5%) 1/52 (1.9%) 1/55 (1.8%)
    Alopecia 16/55 (29.1%) 19/52 (36.5%) 18/55 (32.7%)
    Dermatitis acneiform 2/55 (3.6%) 5/52 (9.6%) 5/55 (9.1%)
    Dermatitis allergic 1/55 (1.8%) 3/52 (5.8%) 1/55 (1.8%)
    Drug eruption 7/55 (12.7%) 5/52 (9.6%) 7/55 (12.7%)
    Dry skin 0/55 (0%) 2/52 (3.8%) 4/55 (7.3%)
    Eczema 4/55 (7.3%) 0/52 (0%) 1/55 (1.8%)
    Erythema multiforme 5/55 (9.1%) 1/52 (1.9%) 1/55 (1.8%)
    Hyperhidrosis 2/55 (3.6%) 3/52 (5.8%) 2/55 (3.6%)
    Palmar-plantar erythrodysaesthesia syndrome 35/55 (63.6%) 37/52 (71.2%) 42/55 (76.4%)
    Pruritus 7/55 (12.7%) 7/52 (13.5%) 9/55 (16.4%)
    Pruritus generalized 1/55 (1.8%) 3/52 (5.8%) 2/55 (3.6%)
    Rash 7/55 (12.7%) 3/52 (5.8%) 4/55 (7.3%)
    Rash maculo-papular 2/55 (3.6%) 1/52 (1.9%) 3/55 (5.5%)
    Vascular disorders
    Hypertension 20/55 (36.4%) 13/52 (25%) 19/55 (34.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Contact for Clinical Trial Information
    Organization Daiichi Sankyo
    Phone 908-992-6400
    Email CTRinfo@dsi.com
    Responsible Party:
    Daiichi Sankyo, Inc.
    ClinicalTrials.gov Identifier:
    NCT01033240
    Other Study ID Numbers:
    • CS1008-A-U204
    First Posted:
    Dec 16, 2009
    Last Update Posted:
    Apr 8, 2021
    Last Verified:
    Apr 1, 2021