Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma (SEARCH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00901901
Recruitment Status : Active, not recruiting
First Posted : May 14, 2009
Results First Posted : September 30, 2013
Last Update Posted : March 9, 2018
Information provided by (Responsible Party):

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Sorafenib (Nexavar, BAY43-9006) + Erlotinib, Tarceva Phase 3

Detailed Description:
European quality of life scale (5 dimensions) (EQ-5D)

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 732 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 21, 2009
Actual Primary Completion Date : April 17, 2012
Estimated Study Completion Date : March 31, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva)
Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd)
Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg twice daily + matching erlotinib placebo daily
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)
Drug: Sorafenib (Nexavar, BAY43-9006) + Erlotinib, Tarceva
Sorafenib 400 mg twice daily + erlotinib 150 mg daily

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: From randomization of the first patient until 34 months or date of death of any cause whichever came first ]
    Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.

Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Disease Control [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ]
    Disease control was defined as the number of participants who had a best response rating of complet 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.

  3. 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. ]
    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.

  4. 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. ]
    Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day.

Other Outcome Measures:
  1. Duration of Response [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ]
    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.

  2. Time to Response [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ]
    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).

  3. Tumor Response [ Time Frame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks ]
    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).

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00901901

  Hide Study Locations
United States, California
San Francisco, California, United States, 94115
United States, District of Columbia
Washington, District of Columbia, United States, 20007
United States, Florida
Gainesville, Florida, United States, 32610
Miami, Florida, United States, 33136
United States, Georgia
Atlanta, Georgia, United States, 30318
United States, Hawaii
Honolulu, Hawaii, United States, 96817
United States, Illinois
Maywood, Illinois, United States, 60153-5585
United States, Kansas
Westwood, Kansas, United States, 66205
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Louisiana
New Orleans, Louisiana, United States, 70112
United States, Maryland
Baltimore, Maryland, United States, 21202
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215-5450
Worcester, Massachusetts, United States, 01655
United States, Michigan
Detroit, Michigan, United States, 48202
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
New York, New York, United States, 10029
Rochester, New York, United States, 14642
Valhalla, New York, United States, 10595
United States, North Carolina
Charlotte, North Carolina, United States, 28203
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98109-1023
Australia, New South Wales
Randwick, New South Wales, Australia, 2031
Australia, Queensland
Brisbane, Queensland, Australia, 4120
Herston, Queensland, Australia, 4029
Australia, Victoria
Clayton, Victoria, Australia, 3168
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Nedlands, Western Australia, Australia, 6009
Wien, Austria, 1090
Bruxelles - Brussel, Belgium, 1200
Edegem, Belgium, 2650
Gent, Belgium, 9000
Kortrijk, Belgium, 8500
La Louviere, Belgium, 7100
Leuven, Belgium, 3000
Liege, Belgium, 4000
Belo Horizonte, Minas Gerais, Brazil, 30110-090
Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
São Paulo, Sao Paulo, Brazil, 05651-900
Rio de Janeiro, Brazil, 21941-913
Sao Paulo, Brazil, 01509-900
Sao Paulo, Brazil, 05403-000
Plovdiv, Bulgaria, 4002
Sofia, Bulgaria, 1784
Varna, Bulgaria, 9002
Varna, Bulgaria, 9010
Canada, Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Quebec
Montreal, Quebec, Canada, H3A 1A1
Santiago, Chile, 7601003
Santiago, Chile, 838-0455
China, Guangdong
Guangzhou, Guangdong, China, 510060
China, Jiangsu
Nanjing, Jiangsu, China, 210002
China, Zhejiang
Hangzhou, Zhejiang, China, 310016
Beijing, China, 100021
Beijing, China, 100071
Floridablanca, Colombia
Medellín, Colombia
Bordeaux, France, 33000
Clichy, France, 92110
Creteil, France, 94010
La Roche Sur Yon, France, 85925
Lille, France, 59037
Lyon, France, 69004
Marseille, France, 13005
Paris, France, 75012
Pessac, France, 33604
Vandoeuvre-les-nancy, France, 54511
Villejuif, France, 94800
Freiburg, Baden-Württemberg, Germany, 79106
Tübingen, Baden-Württemberg, Germany, 72076
München, Bayern, Germany, 81675
Regensburg, Bayern, Germany, 93042
Frankfurt, Hessen, Germany, 60590
Hannover, Niedersachsen, Germany, 30625
Essen, Nordrhein-Westfalen, Germany, 45147
Köln, Nordrhein-Westfalen, Germany, 50937
Mainz, Rheinland-Pfalz, Germany, 55131
Homburg, Saarland, Germany, 66421
Berlin, Germany, 12200
Athens, Greece, 115 27
Larissa, Greece, 41100
Thessaloniki, Greece, 546 36
Thessaloniki, Greece, 54642
Hong Kong
Hong Kong, Hong Kong
Shatin, Hong Kong
Beer Sheva, Israel, 8410101
Haifa, Israel, 3109601
Petah Tikva, Israel, 4941492
Rehovot, Israel, 7610001
Zrifin, Israel, 6093000
Milano, Lombardia, Italy, 20089
Korea, Republic of
Goyang-si, Gyeonggido, Korea, Republic of, 410-769
Seoul, Korea, Republic of, 110-744
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 138-736
Seoul, Korea, Republic of, 152-703
New Zealand
Auckland, New Zealand, 1023
Christchurch, New Zealand, 8011
Wellington South, New Zealand, 6021
Lima, Peru, LIMA 1
Lima, Peru, LIMA 34
Bydgoszcz, Poland, 85-796
Gdansk, Poland, 80-952
Gliwice, Poland, 44-101
Warszawa, Poland, 02-781
Russian Federation
Barnaul, Russian Federation, 656049
Moscow, Russian Federation, 115478
Nizhny Novgorod, Russian Federation, 603001
Singapore, Singapore, 169610
Singapore, Singapore, 308433
South Africa
Johannesburg, Gauteng, South Africa, 2193
Cape Town, Western Cape, South Africa, 7500
Hospitalet de Llobregat, Barcelona, Spain, 08907
Barcelona, Spain, 08036
Lugo, Spain, 27003
Madrid, Spain, 28040
Santander, Spain, 39008
Valencia, Spain, 46010
Valencia, Spain, 46026
Tainan, Taiwan, 736
Taipei, Taiwan, 112
Taoyuan, Taiwan, 333
United Kingdom
Sheffield, South Yorkshire, United Kingdom, S10 2SJ
Glasgow, United Kingdom, G12 0YN
London, United Kingdom, SE5 9RS
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer Identifier: NCT00901901     History of Changes
Other Study ID Numbers: 12917
2008-006021-14 ( EudraCT Number )
First Posted: May 14, 2009    Key Record Dates
Results First Posted: September 30, 2013
Last Update Posted: March 9, 2018
Last Verified: February 2018

Keywords provided by Bayer:
Sorafenib (Nexavar)
Erlotinib (Tarceva)
First Line

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs