- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00901901
Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma (SEARCH)
May 16, 2019 updated by: Bayer
A Phase III Randomized, Placebo Controlled, Double Blind Trial of Sorafenib Plus Erlotinib vs. Sorafenib Plus Placebo as First Line Systemic Treatment for Hepatocellular Carcinoma (HCC)
This is a randomized trial to evaluate the clinical benefit of sorafenib 400 mg twice daily and erlotinib 150 mg once a day versus sorafenib 400 mg twice daily and placebo erlotinib once daily in subjects with unresectable advanced or metastatic Child-Pugh A HCC. Patients who are candidates for potentially curative intervention (i.e.
surgical resection or local ablation) are not eligible for this study.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
European quality of life scale (5 dimensions) (EQ-5D)
Study Type
Interventional
Enrollment (Actual)
732
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Randwick, New South Wales, Australia, 2031
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Queensland
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Brisbane, Queensland, Australia, 4120
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Herston, Queensland, Australia, 4029
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Victoria
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Clayton, Victoria, Australia, 3168
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Melbourne, Victoria, Australia, 3004
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Western Australia
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Nedlands, Western Australia, Australia, 6009
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Wien, Austria, 1090
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Bruxelles - Brussel, Belgium, 1200
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Edegem, Belgium, 2650
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Gent, Belgium, 9000
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Kortrijk, Belgium, 8500
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La Louviere, Belgium, 7100
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Leuven, Belgium, 3000
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Liege, Belgium, 4000
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Rio de Janeiro, Brazil, 21941-913
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Sao Paulo, Brazil, 01509-900
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Sao Paulo, Brazil, 05403-000
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Minas Gerais
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Belo Horizonte, Minas Gerais, Brazil, 30110-090
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Rio Grande Do Sul
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Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
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Sao Paulo
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São Paulo, Sao Paulo, Brazil, 05651-900
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Plovdiv, Bulgaria, 4002
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Sofia, Bulgaria, 1784
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Varna, Bulgaria, 9002
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Varna, Bulgaria, 9010
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Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
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Quebec
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Montreal, Quebec, Canada, H3A 1A1
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Santiago, Chile, 7601003
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Santiago, Chile, 838-0455
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Beijing, China, 100021
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Beijing, China, 100071
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Guangdong
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Guangzhou, Guangdong, China, 510060
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Jiangsu
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Nanjing, Jiangsu, China, 210002
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Zhejiang
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Hangzhou, Zhejiang, China, 310016
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Floridablanca, Colombia
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Medellín, Colombia
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Bordeaux, France, 33000
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Clichy, France, 92110
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Creteil, France, 94010
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La Roche Sur Yon, France, 85925
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Lille, France, 59037
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Lyon, France, 69004
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Marseille, France, 13005
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Paris, France, 75012
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Pessac, France, 33604
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Vandoeuvre-les-nancy, France, 54511
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Villejuif, France, 94800
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Berlin, Germany, 12200
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Baden-Württemberg
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Freiburg, Baden-Württemberg, Germany, 79106
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Tübingen, Baden-Württemberg, Germany, 72076
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Bayern
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München, Bayern, Germany, 81675
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Regensburg, Bayern, Germany, 93042
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Hessen
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Frankfurt, Hessen, Germany, 60590
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Niedersachsen
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Hannover, Niedersachsen, Germany, 30625
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Nordrhein-Westfalen
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Essen, Nordrhein-Westfalen, Germany, 45147
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Köln, Nordrhein-Westfalen, Germany, 50937
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Rheinland-Pfalz
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Mainz, Rheinland-Pfalz, Germany, 55131
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Saarland
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Homburg, Saarland, Germany, 66421
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Athens, Greece, 115 27
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Larissa, Greece, 41100
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Thessaloniki, Greece, 54642
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Thessaloniki, Greece, 546 36
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Hong Kong, Hong Kong
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Shatin, Hong Kong
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Beer Sheva, Israel, 8410101
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Haifa, Israel, 3109601
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Petah Tikva, Israel, 4941492
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Rehovot, Israel, 7610001
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Zrifin, Israel, 70300
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Lombardia
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Milano, Lombardia, Italy, 20089
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Seoul, Korea, Republic of, 03080
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Seoul, Korea, Republic of, 05505
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Seoul, Korea, Republic of, 06351
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Seoul, Korea, Republic of, 152-703
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Gyeonggido
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Goyang-si, Gyeonggido, Korea, Republic of, 410-769
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Auckland, New Zealand, 1023
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Christchurch, New Zealand, 8011
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Wellington South, New Zealand, 6021
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Lima, Peru, Lima 1
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Lima, Peru, LIMA 34
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Bydgoszcz, Poland, 85-796
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Gdansk, Poland, 80-952
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Gliwice, Poland, 44-101
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Warszawa, Poland, 02-781
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Barnaul, Russian Federation, 656049
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Moscow, Russian Federation, 115478
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Nizhny Novgorod, Russian Federation, 603001
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Singapore, Singapore, 308433
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Singapore, Singapore, 169610
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Gauteng
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Johannesburg, Gauteng, South Africa, 2193
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Western Cape
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Cape Town, Western Cape, South Africa, 7500
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Barcelona, Spain, 08036
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Lugo, Spain, 27003
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Madrid, Spain, 28040
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Santander, Spain, 39008
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Valencia, Spain, 46026
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Valencia, Spain, 46010
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Barcelona
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Hospitalet de Llobregat, Barcelona, Spain, 08907
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Tainan, Taiwan, 736
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Taipei, Taiwan, 112
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Taoyuan, Taiwan, 333
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Glasgow, United Kingdom, G12 0YN
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London, United Kingdom, SE5 9RS
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Newcastle Upon Tyne, United Kingdom, NE7 7DN
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South Yorkshire
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Sheffield, South Yorkshire, United Kingdom, S10 2SJ
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California
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San Francisco, California, United States, 94115
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District of Columbia
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Washington, District of Columbia, United States, 20007
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Florida
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Gainesville, Florida, United States, 32610
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Miami, Florida, United States, 33136
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Georgia
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Atlanta, Georgia, United States, 30318
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Hawaii
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Honolulu, Hawaii, United States, 96817
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Illinois
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Maywood, Illinois, United States, 60153-5585
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Kansas
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Westwood, Kansas, United States, 66205
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Kentucky
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Louisville, Kentucky, United States, 40202
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Louisiana
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New Orleans, Louisiana, United States, 70112
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Maryland
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Baltimore, Maryland, United States, 21202
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Massachusetts
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Boston, Massachusetts, United States, 02114
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Boston, Massachusetts, United States, 02215-5450
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Worcester, Massachusetts, United States, 01655
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Michigan
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Detroit, Michigan, United States, 48202
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Minnesota
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Minneapolis, Minnesota, United States, 55455
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New York
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New York, New York, United States, 10029
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Rochester, New York, United States, 14642
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Valhalla, New York, United States, 10595
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North Carolina
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Charlotte, North Carolina, United States, 28203
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19107
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Texas
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Houston, Texas, United States, 77030
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Washington
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Seattle, Washington, United States, 98109-1023
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients > 18 years of age
- Patients who have a life expectancy of at least 12 weeks
- Patients with histological or cytologically documented HCC
Patients must have at least one tumor lesion that meets both of the following criteria:
- The lesion can be accurately measured in at least one dimension according to response evaluation criteria in solid tumors (RECIST)
- The lesion has not been previously treated with local therapy
- Patients who have an ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1
- Cirrhotic status of Child-Pugh class A.
- Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time.
Exclusion Criteria:
- History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin), or uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted.
- Abnormalities of the cornea based on history (e.g. dry eye syndrome, Sogren's syndrome) including congenital abnormality (e.g. Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g. fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test).
- History of interstitial lung disease (ILD).
- Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
- Previous treatment with yttrium-90 spheres
- Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
- Uncontrolled ascites (defined as not easily controlled with diuretic treatment)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva)
Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd)
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Sorafenib 400 mg twice daily
Erlotinib 150 mg once daily
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ACTIVE_COMPARATOR: Sorafenib (Nexavar, BAY43-9006) + Placebo
Participants received sorafenib 400 mg twice daily (bid) and matching erlotinib placebo 150 mg tablet once daily (qd)
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Sorafenib 400 mg twice daily
Matching erlotinib placebo 150 mg once daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Survival
Time Frame: From randomization of the first patient until 34 months or date of death of any cause whichever came first
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Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.
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From randomization of the first patient until 34 months or date of death of any cause whichever came first
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Time to Radiological Tumor Progression (TTP)
Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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TTP was the time from randomization to radiological tumor progression.
Participants without radiological tumor progression at the time of analysis were censored at their last date of tumor evaluation.
Progressive disease (PD) was defined using Response Evaluation Criteria in Solid Tumors (RECIST version 1.0), as at least a 20% increase in the sum of longest diameter (LD) of measured lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Appearance of new lesions also constituted PD.
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From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Disease Control
Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Disease control was defined as the number of participants who had a best response rating of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST assessed by magnetic resonance imaging (MRI) that was confirmed at least 28 days from the first demonstration of that rating.
CR: disappearance of all clinical and radiological evidence of target and non-target tumors.
PR: at least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD.
SD: steady state of disease.
Neither sufficient shrinkage for PR nor sufficient increase for PD.
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From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Health-related Quality of Life and Utility Values as Measured by EQ-5D - Index
Time Frame: The EQ-5D was administered at the beginning of the visit prior to seeing the investigator. Questionnaires were to be completed every 6 weeks (Day 1 of each cycle) for subsequent cycles and at the end of treatment visit.
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The European quality of life scale (5 dimensions) (EQ-5D) questionnaire was given to the participants at each visit.
The EQ-5D questionnaire consisted of 5 ordinal categorical responses (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).
The scores for the EQ-5D dimensions are assigned according to the level of problems reported (1 'no problems'; 2 'some problems'; 3 'extreme problems').
The 5 health dimensions are summarized into a single score, the EQ-5D index score.
The EQ-5D index score has a range of 0 and 1 with 0 representing death and 1 representing perfect health.
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The EQ-5D was administered at the beginning of the visit prior to seeing the investigator. Questionnaires were to be completed every 6 weeks (Day 1 of each cycle) for subsequent cycles and at the end of treatment visit.
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Health-related Quality of Life and Utility Values as Measured by EQ-5D - VAS
Time Frame: The EQ-5D VAS was administered at the beginning of the visit prior to seeing the investigator. Questionnaires were to be completed every 6 weeks (Day 1 of each cycle) for subsequent cycles and at the end of treatment visit.
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Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day.
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The EQ-5D VAS was administered at the beginning of the visit prior to seeing the investigator. Questionnaires were to be completed every 6 weeks (Day 1 of each cycle) for subsequent cycles and at the end of treatment visit.
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Duration of Response
Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Duration of response - RECIST: number of days from the date that CR or PR is first documented to date that PD is first objectively documented or to death before progression.
Note: the relevant date is that of the first documentation, not the confirmation date (if participant progressed or died then censored=no) or to last observation if participant did not progress or die then censored=yes note: this last observation date should be the same as that used for time to progression.
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From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Time to Response
Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Time to response was the number of days from randomization to the date the CR or PR was documented (with confirmation) (Note: the relevant date is that of the first documentation, not the confirmation date).
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From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Tumor Response
Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Tumor response was the proportion of participants with the best tumor response (ie, achieving either a confirmed complete response [CR] or partial response [PR], according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria).
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From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
May 21, 2009
Primary Completion (ACTUAL)
April 17, 2012
Study Completion (ACTUAL)
May 23, 2018
Study Registration Dates
First Submitted
May 13, 2009
First Submitted That Met QC Criteria
May 13, 2009
First Posted (ESTIMATE)
May 14, 2009
Study Record Updates
Last Update Posted (ACTUAL)
May 30, 2019
Last Update Submitted That Met QC Criteria
May 16, 2019
Last Verified
May 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
- Sorafenib
Other Study ID Numbers
- 12917
- 2008-006021-14 (EUDRACT_NUMBER)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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