Back to resultsNexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma (SEARCH)
Primary Purpose
Carcinoma, Hepatocellular
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sorafenib (Nexavar, BAY43-9006)
Erlotinib (Tarceva)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Sorafenib (Nexavar), Erlotinib (Tarceva), First Line, HCC
Eligibility Criteria
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva)
Sorafenib (Nexavar, BAY43-9006) + Placebo
Arm Description
Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd)
Participants received sorafenib 400 mg twice daily (bid) and matching erlotinib placebo 150 mg tablet once daily (qd)
Outcomes
Primary Outcome Measures
Overall Survival
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.
Secondary Outcome Measures
Time to Radiological Tumor Progression (TTP)
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.
Disease Control
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.
Health-related Quality of Life and Utility Values as Measured by EQ-5D - Index
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.
Health-related Quality of Life and Utility Values as Measured by EQ-5D - VAS
Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00901901
Brief Title
Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma
Acronym
SEARCH
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
May 21, 2009 (Actual)
Primary Completion Date
April 17, 2012 (Actual)
Study Completion Date
May 23, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
European quality of life scale (5 dimensions) (EQ-5D)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Sorafenib (Nexavar), Erlotinib (Tarceva), First Line, HCC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
732 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib (Nexavar, BAY43-9006) + Erlotinib (Tarceva)
Arm Type
Experimental
Arm Description
Participants received sorafenib 400 mg twice daily (bid) and erlotinib 150 mg tablet once daily (qd)
Arm Title
Sorafenib (Nexavar, BAY43-9006) + Placebo
Arm Type
Active Comparator
Arm Description
Participants received sorafenib 400 mg twice daily (bid) and matching erlotinib placebo 150 mg tablet once daily (qd)
Intervention Type
Drug
Intervention Name(s)
Sorafenib (Nexavar, BAY43-9006)
Intervention Description
Sorafenib 400 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Erlotinib (Tarceva)
Intervention Description
Erlotinib 150 mg once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching erlotinib placebo 150 mg once daily
Primary Outcome Measure Information:
Title
Overall Survival
Description
Overall Survival (OS) was defined as the time from date of randomization to death due to any cause.
Time Frame
From randomization of the first patient until 34 months or date of death of any cause whichever came first
Secondary Outcome Measure Information:
Title
Time to Radiological Tumor Progression (TTP)
Description
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.
Time Frame
From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
Title
Disease Control
Description
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.
Time Frame
From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
Title
Health-related Quality of Life and Utility Values as Measured by EQ-5D - Index
Description
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.
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.
Title
Health-related Quality of Life and Utility Values as Measured by EQ-5D - VAS
Description
Participants indicated on a scale of 0 (worst) to 100 (best) how good or bad their health state was on that particular day.
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.
Other Pre-specified Outcome Measures:
Title
Duration of Response
Description
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.
Time Frame
From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
Title
Time to Response
Description
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).
Time Frame
From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
Title
Tumor Response
Description
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).
Time Frame
From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96817
Country
United States
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153-5585
Country
United States
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215-5450
Country
United States
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4120
Country
Australia
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
City
Wien
ZIP/Postal Code
1090
Country
Austria
City
Bruxelles - Brussel
ZIP/Postal Code
1200
Country
Belgium
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
City
La Louviere
ZIP/Postal Code
7100
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30110-090
Country
Brazil
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90020-090
Country
Brazil
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
05651-900
Country
Brazil
City
Rio de Janeiro
ZIP/Postal Code
21941-913
Country
Brazil
City
Sao Paulo
ZIP/Postal Code
01509-900
Country
Brazil
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1784
Country
Bulgaria
City
Varna
ZIP/Postal Code
9002
Country
Bulgaria
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
City
Santiago
ZIP/Postal Code
7601003
Country
Chile
City
Santiago
ZIP/Postal Code
838-0455
Country
Chile
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
City
Beijing
ZIP/Postal Code
100021
Country
China
City
Beijing
ZIP/Postal Code
100071
Country
China
City
Floridablanca
Country
Colombia
City
Medellín
Country
Colombia
City
Bordeaux
ZIP/Postal Code
33000
Country
France
City
Clichy
ZIP/Postal Code
92110
Country
France
City
Creteil
ZIP/Postal Code
94010
Country
France
City
La Roche Sur Yon
ZIP/Postal Code
85925
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Lyon
ZIP/Postal Code
69004
Country
France
City
Marseille
ZIP/Postal Code
13005
Country
France
City
Paris
ZIP/Postal Code
75012
Country
France
City
Pessac
ZIP/Postal Code
33604
Country
France
City
Vandoeuvre-les-nancy
ZIP/Postal Code
54511
Country
France
City
Villejuif
ZIP/Postal Code
94800
Country
France
City
Freiburg
State/Province
Baden-Württemberg
ZIP/Postal Code
79106
Country
Germany
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
City
München
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93042
Country
Germany
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45147
Country
Germany
City
Köln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50937
Country
Germany
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
City
Berlin
ZIP/Postal Code
12200
Country
Germany
City
Athens
ZIP/Postal Code
115 27
Country
Greece
City
Larissa
ZIP/Postal Code
41100
Country
Greece
City
Thessaloniki
ZIP/Postal Code
546 36
Country
Greece
City
Thessaloniki
ZIP/Postal Code
54642
Country
Greece
City
Hong Kong
Country
Hong Kong
City
Shatin
Country
Hong Kong
City
Beer Sheva
ZIP/Postal Code
8410101
Country
Israel
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
City
Petah Tikva
ZIP/Postal Code
4941492
Country
Israel
City
Rehovot
ZIP/Postal Code
7610001
Country
Israel
City
Zrifin
ZIP/Postal Code
70300
Country
Israel
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
City
Goyang-si
State/Province
Gyeonggido
ZIP/Postal Code
410-769
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
152-703
Country
Korea, Republic of
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
City
Wellington South
ZIP/Postal Code
6021
Country
New Zealand
City
Lima
ZIP/Postal Code
LIMA 1
Country
Peru
City
Lima
ZIP/Postal Code
LIMA 34
Country
Peru
City
Bydgoszcz
ZIP/Postal Code
85-796
Country
Poland
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
City
Gliwice
ZIP/Postal Code
44-101
Country
Poland
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
City
Barnaul
ZIP/Postal Code
656049
Country
Russian Federation
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
City
Nizhny Novgorod
ZIP/Postal Code
603001
Country
Russian Federation
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7500
Country
South Africa
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Lugo
ZIP/Postal Code
27003
Country
Spain
City
Madrid
ZIP/Postal Code
28040
Country
Spain
City
Santander
ZIP/Postal Code
39008
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain
City
Tainan
ZIP/Postal Code
736
Country
Taiwan
City
Taipei
ZIP/Postal Code
112
Country
Taiwan
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
City
Sheffield
State/Province
South Yorkshire
ZIP/Postal Code
S10 2SJ
Country
United Kingdom
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
Learn more about this trial
Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma
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