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A Study of Ramucirumab (IMC-1121B) Drug Product (DP) and Best Supportive Care (BSC) Versus Placebo and BSC as 2nd-Line Treatment in Patients With Hepatocellular Carcinoma After 1st-Line Therapy With Sorafenib (REACH)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01140347
First received: June 2, 2010
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

This is a Phase 3 multicenter, randomized study evaluating the safety and efficacy of ramucirumab DP plus BSC as a double-blind, placebo-controlled (placebo plus BSC) comparison.

Approximately 544 patients, at least 18 years of age, with Child-Pugh score < 7 and diagnosed with hepatocellular carcinoma will be randomized. Patients must have received sorafenib as first-line systemic treatment for HCC, and must have discontinued sorafenib prior to entering the study.

Hypothesis: This sample size will allow differentiation of the expected increase in median OS, from 8 months in the placebo arm to 10.67 months in the ramucirumab arm.

Upon registration and completion of screening procedures, eligible patients with HCC who have disease progression during or following first-line therapy with sorafenib, or were intolerant to this agent, will be randomized to receive either ramucirumab DP or placebo.

The treatment regimen will be continued until radiographic or symptomatic progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the patient, or investigator decision.


Condition Intervention Phase
Hepatocellular Carcinoma
Biological: Placebo
Biological: Ramucirumab DP (IMC-1121B)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Phase 3 Study of Ramucirumab (IMC-1121B) Drug Product and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma Following First-Line Therapy With Sorafenib (REACH)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Overall survival (OS) - Time from the date of randomization to the date of death from any cause [ Time Frame: Approximately 43 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Approximately 43 months ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) [ Time Frame: Approximately 43 months ] [ Designated as safety issue: No ]
  • Time to radiographic progression [ Time Frame: Approximately 43 months ] [ Designated as safety issue: No ]
  • Change in the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8) [ Time Frame: Approximately 43 months ] [ Designated as safety issue: No ]
  • Change in EuroQol EQ-5D, change from baseline in the patient reported outcomes measured at the end of therapy visit [ Time Frame: Approximately 43 months ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 43 months ] [ Designated as safety issue: Yes ]
  • Maximum concentration (Cmax) cycle 1 [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) cycle 4 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Maximum concentration (Cmax) cycle 7 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Serum Anti-ramucirumab Antibody Assessment (Immunogenicity) [ Time Frame: Approximately 43 months ] [ Designated as safety issue: Yes ]

Enrollment: 565
Study Start Date: October 2010
Estimated Study Completion Date: July 2015
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramucirumab DP
Ramucirumab DP (IMC-1121B)
Biological: Ramucirumab DP (IMC-1121B)
8 mg/kg I.V. every 2 weeks
Other Names:
  • IMC-1121B
  • LY3009806
Placebo Comparator: Placebo
Placebo
Biological: Placebo
8 mg/kg I.V. infusion every 2 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Child-Pugh score of < 7 (Child-Pugh Class A only)
  • Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to locoregional therapy or refractory to locoregional therapy
  • Diagnosis of HCC (excluding fibrolamellar carcinoma) in the absence of histologic or cytologic confirmation
  • There are either clinical, laboratory, or radiographic findings consistent with a diagnosis of liver cirrhosis
  • Has a liver mass measuring at least 2 cm with characteristic vascularization seen on either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) with gadolinium
  • At least 1 measurable or evaluable lesion that is viable (ie, is vascularized), and has not been previously treated with locoregional therapy. A lesion that has been previously treated will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy
  • Previously treated with sorafenib and has discontinued sorafenib treatment at least 14 days prior to randomization. patients may have experienced:

    • Radiographically documented disease progression during sorafenib therapy or after discontinuation of sorafenib therapy, or
    • Discontinuation of sorafenib due to an adverse drug reaction, despite dose reduction by 1 level and BSC
  • The patient has received sorafenib as the only systemic therapeutic intervention. Any hepatic locoregional therapy that has been administered prior to sorafenib is allowed, but not following sorafenib. Radiation to metastatic sites (eg, bone) following sorafenib therapy is permitted.
  • Resolution of clinically significant toxicity of any anti cancer therapy to grade ≤ 1 by the NCI-CTCAE v. 4.0

Adequate Organ Function defined as:

  • Total bilirubin < 3.0 mg/dL (51.3 µmol/L), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN
  • Serum creatinine ≤ 1.2 × ULN or calculated creatinine clearance > 50 mL/minute
  • Absolute neutrophil count (ANC) ≥ 1.0 × 10^3/μL (1.0 × 10^9/L), hemoglobin ≥ 9 g/dL (5.58 mmol/L), and platelets ≥ 75 × 10^3/µL (75 × 10^9/L)
  • International Normalized Ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 5 seconds above ULN. Patients receiving prophylactic low-dose anticoagulant therapy are eligible provided that INR ≤ 1.5 and PTT ≤ 5 seconds above the upper limit of normal (ULN)
  • The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study

Exclusion criteria:

  • Major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to randomization
  • Hepatic locoregional therapy within 28 days prior to randomization
  • Radiation to any nonhepatic (eg, bone) site within 14 days prior to randomization
  • Sorafenib within 14 days prior to randomization
  • Received any investigational therapy or non-approved drug within 28 days prior to randomization
  • Received any previous systemic therapy with vascular endothelial growth factor (VEGF) inhibitors or vascular endothelial growth factor receptor (VEGFR) inhibitors (including investigational agents) other than sorafenib for treatment of HCC
  • Fibrolamellar carcinoma
  • Received any transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte colony-stimulating factors (G-CSF) within 14 days prior to randomization
  • Therapeutic anticoagulation with warfarin, low-molecular-weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria(INR ≤ 1.5 and PTT ≤ 5 seconds above the upper limit of normal [ULN]) are met
  • Receiving ongoing therapy with nonsteroidal anti-inflammatory agents (NSAIDs, eg, indomethacin, ibuprofen, naproxen, nimesulide, celecoxib, etoricoxib, or similar agents) or other antiplatelet agents (eg, clopidogrel, ticlopidine, prasugrel, dipyridamole, picotamide, indobufen, anagrelide, triflusal).Aspirin (ASA) at doses up to 100 mg/day is permitted
  • Symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia
  • Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization
  • Uncontrolled arterial hypertension ≥ 150 / ≥ 90 mm Hg despite standard medical management
  • Grade 3-4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to randomization requiring transfusion, endoscopic or operative intervention (patients with any bleeding episode considered life-threatening during the 3 months prior to randomization are excluded, regardless of transfusion or intervention status)
  • Esophageal or gastric varices that require immediate intervention (eg, banding, sclerotherapy) or represent a high bleeding risk. Patients with evidence of portal hypertension (including splenomegaly) or any prior history of variceal bleeding must have had endoscopic evaluation within the 3 months immediately prior to randomization. Patients with evidence of portal hypertension are eligible for study participation if endoscopic evaluation does not indicate esophageal or gastric varices that require immediate intervention or represent a high bleeding risk; however, these eligible patients must receive supportive therapy (eg, beta blocker therapy) according to institutional standards and clinical guidelines during study participation
  • Central nervous system (CNS) metastases or carcinomatous meningitis
  • History of or current hepatic encephalopathy or current clinically meaningful ascites
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01140347

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Locations
United States, California
ImClone Investigational Site
Orange, California, United States, 92868
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San Francisco, California, United States, 94115
United States, Connecticut
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New Haven, Connecticut, United States, 06520
United States, Florida
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Jacksonville, Florida, United States, 32207
United States, Louisiana
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New Orleans, Louisiana, United States, 70112
United States, Massachusetts
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Boston, Massachusetts, United States, 02111
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Worcester, Massachusetts, United States, 01655
United States, Michigan
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Ann Arbor, Michigan, United States, 48109
United States, Missouri
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St Louis, Missouri, United States, 63110
United States, New Jersey
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Newark, New Jersey, United States, 07103
United States, New York
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New York, New York, United States, 10029
United States, North Carolina
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Winston-Salem, North Carolina, United States, 27157
United States, Ohio
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Dayton, Ohio, United States, 45420
United States, Pennsylvania
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Philadelphia, Pennsylvania, United States, 19141
United States, South Carolina
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Charleston, South Carolina, United States, 29414
United States, Texas
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Lubbock, Texas, United States, 79415
United States, Washington
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Seattle, Washington, United States, 98109
United States, Wisconsin
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Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
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Bankstown, New South Wales, Australia, 2200
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Kogarah, New South Wales, Australia, 2217
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Liverpool Bc, New South Wales, Australia, 1871
Australia, South Australia
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Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
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Prahran, Victoria, Australia, 3181
Austria
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Linz, Austria, 4021
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Salzburg, Austria, 5020
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Steyr, Austria, 4400
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Vienna, Austria, A1090
Belgium
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Bonheiden, Belgium, 2820
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Brussels, Belgium, 01200
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Charleroi, Belgium, 6000
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Edegem, Belgium, 2650
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Leuven, Belgium, 03000
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Liège, Belgium, 4000
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Ottignies, Belgium, 1340
Brazil
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Belo Horizonte, Brazil, 30110090
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Botucatu, Brazil, 18618-970
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Brasilia, Brazil, 72115-700
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Campinas, Brazil, 13083-970
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Ijui, Brazil, 98700 000
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Ribeirao Preto, Brazil, 14049-900
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Rio De Janeiro, Brazil, 21941-31
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Salvador, Brazil, 41825-010
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Sao Jose Rio Preto, Brazil, 15090-000
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São Paulo, Brazil, 04039-901
Bulgaria
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Plovdiv, Bulgaria, 4004
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Sofia, Bulgaria, 1527
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Varna, Bulgaria, 9010
Canada, Ontario
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Ottawa, Ontario, Canada, K1H 8L6
Czech Republic
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Brib, Czech Republic, 656 53
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Hradec Kralove, Czech Republic, 500 05
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Olomouc, Czech Republic, 775 20
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Prague, Czech Republic, 150 06
Finland
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Helsinki, Finland, 180
France
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Amiens, France, 80054
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Angers, France, 49933
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Avignon, France, 84000
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Besancon, France, 25020
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Bordeaux, France, 33000
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Clermont-Ferrand, France, 63003
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La Roche Sur Yon, France, 85925
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Limoges, France, 87042
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Marseille, France, 13385
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Nice, France, 06200
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Paris, France, 75674
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Poitiers, France, 86021
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Reims, France, 51092
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Saint-Etienne, France, 42055
Germany
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Berlin, Germany, 12203
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Bielefeld, Germany, 33611
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Bonn, Germany, 53105
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Düsseldorf, Germany, 40225
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Essen, Germany, 45122
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Frankfurt, Germany, 60596
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Freiburg, Germany, 79106
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Hamburg, Germany, 20246
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Hannover, Germany, 30625
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Homburg, Germany, 66421
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Leipzig, Germany, 04103
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Magdeburg, Germany, 39120
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Munich, Germany, 81377
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Münster, Germany, 48149
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Tübingen, Germany, 72076
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Ulm, Germany, 89081
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Weiden, Germany, 92637
Hong Kong
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Kowloon, Hong Kong
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Pokfulam, Hong Kong
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Shatin, Hong Kong
Hungary
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Budapest, Hungary, 1122
Israel
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Beer Sheva, Israel, 84101
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Petah Tiqva, Israel, 49100
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Tel Aviv, Israel, 64239
Italy
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Bari, Italy, 70124
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Benevento, Italy, 82100
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Bologna, Italy, 40100
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Genova, Italy, 16132
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Lecce, Italy, 73100
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Milano, Italy, 20122
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Modena, Italy, 41100
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Padova, Italy, 35128
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Palermo, Italy, 90127
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Pavia, Italy, 27100
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Rome, Italy, 00168
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Udine, Italy, 33100
Japan
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Chiba, Japan, 260-8677
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Fukuoka, Japan, 810-8563
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Hyogo, Japan, 650-0046
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Ishikawa, Japan, 920-8641
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Kanagawa, Japan, 241-0815
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Kochi, Japan, 781-8555
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Kyoto, Japan, 606-8397
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Miyagi, Japan, 983-8520
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Osaka, Japan, 565-0871
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Osaka-Pref, Japan, 589
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Saga, Japan, 840
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Tochigi, Japan, 329-0498
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Tokushima, Japan, 770-8503
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Tokyo, Japan, 181-8611
Korea, Republic of
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Anyang, Korea, Republic of, 431-070
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Incheon, Korea, Republic of, 405-760
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Seodaemun-Gu, Korea, Republic of, 120-752
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Seoul, Korea, Republic of, 135-710
Netherlands
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Amsterdam, Netherlands, 1105 AZ
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Rotterdam, Netherlands, 3000 CA
Norway
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Oslo, Norway, 0407
Philippines
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Quezon City, Philippines, 1102
Portugal
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Lisbon, Portugal, 1649-035
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Santa Maria Da Feira, Portugal, 4520-211
Romania
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Bucharest, Romania, 022328
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Cluj-Napoca, Romania, 3400
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Craiova, Romania, 200535
Spain
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Avila, Spain, 05004
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Girona, Spain, 17007
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Madrid, Spain, 28041
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Ourense, Spain, 320004
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Valencia, Spain, 46014
Sweden
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Stockholm, Sweden, 14186
Switzerland
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Bern, Switzerland, CH-3010
Taiwan
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Changhua, Taiwan, 500
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Kuei Shan Hsiang, Taiwan, 33305
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Liouying/Tainan, Taiwan, 736
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Niaosung, Taiwan, 883
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Taichung, Taiwan, 404
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Tainan, Taiwan, 70403
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Taipei, Taiwan, 112
Thailand
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Bangkok, Thailand, 10700
ImClone Investigational Site
Hat Yai, Thailand, 90110
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01140347     History of Changes
Other Study ID Numbers: 13895, CP12-0919, I4T-IE-JVBF, 2010-019318-26
Study First Received: June 2, 2010
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Finland: Finnish Medicines Agency
Germany: Paul-Ehrlich-Institut
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Indonesia: National Agency of Drug and Food Control
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Malaysia: Ministry of Health
Netherlands: Ministry of Health, Welfare and Sport
New Zealand: Medsafe
Norway: Norwegian Medicines Agency
Philippines: Bureau of Food and Drugs
Poland: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Singapore: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
South Korea: Korea Food and Drug Administration (KFDA)
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: Department of Health
Thailand: Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Eli Lilly and Company:
Hepatocellular carcinoma (HCC)
recombinant human immunoglobulin G
subclass 1 (IgG1) monoclonal antibody (MAb)
Hepatocellular Carcinoma (HCC) following First-Line Therapy With Sorafenib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014