Clinical trial NCT00901901: Nexavar-Tarceva Combination Therapy for First Line Treatment of Patients Diagnosed With Hepatocellular Carcinoma
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Keywords: Sorafenib (Nexavar)
Erlotinib (Tarceva)
First Line
HCC
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-05-14
Enrollment: 732
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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)

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization of the first patient until 34 months or date of death of any cause whichever came first
Secondary outcomes:
measure: Time to Radiological Tumor Progression (TTP)
timeFrame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
measure: Disease Control
timeFrame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
measure: Health-related Quality of Life and Utility Values as Measured by EQ-5D - Index
timeFrame: 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.
measure: Health-related Quality of Life and Utility Values as Measured by EQ-5D - VAS
timeFrame: 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 outcomes:
measure: Duration of Response
timeFrame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
measure: Time to Response
timeFrame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
measure: Tumor Response
timeFrame: From randomization of the first participant until 34 months later (cut-off date), assessed every 6 weeks
Locations:
city: San Francisco
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Maywood
country: United States
state: Illinois
city: Westwood
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Randwick
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Herston
country: Australia
state: Queensland
city: Clayton
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Wien
country: Austria
city: Bruxelles - Brussel
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: La Louviere
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Belo Horizonte
country: Brazil
state: Minas Gerais
city: Porto Alegre
country: Brazil
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Sao Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Varna
country: Bulgaria
city: Edmonton
country: Canada
state: Alberta
city: Montreal
country: Canada
state: Quebec
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Guangzhou
country: China
state: Guangdong
city: Nanjing
country: China
state: Jiangsu
city: Hangzhou
country: China
state: Zhejiang
city: Beijing
country: China
city: Beijing
country: China
city: Floridablanca
country: Colombia
city: Medellín
country: Colombia
city: Bordeaux
country: France
city: Clichy
country: France
city: Creteil
country: France
city: La Roche Sur Yon
country: France
city: Lille
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Paris
country: France
city: Pessac
country: France
city: Vandoeuvre-les-nancy
country: France
city: Villejuif
country: France
city: Freiburg
country: Germany
state: Baden-Württemberg
city: Tübingen
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Regensburg
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Hannover
country: Germany
state: Niedersachsen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Homburg
country: Germany
state: Saarland
city: Berlin
country: Germany
city: Athens
country: Greece
city: Larissa
country: Greece
city: Thessaloniki
country: Greece
city: Thessaloniki
country: Greece
city: Hong Kong
country: Hong Kong
city: Shatin
country: Hong Kong
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Petah Tikva
country: Israel
city: Rehovot
country: Israel
city: Zrifin
country: Israel
city: Milano
country: Italy
state: Lombardia
city: Goyang-si
country: Korea, Republic of
state: Gyeonggido
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Wellington South
country: New Zealand
city: Lima
country: Peru
city: Lima
country: Peru
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Gliwice
country: Poland
city: Warszawa
country: Poland
city: Barnaul
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Johannesburg
country: South Africa
state: Gauteng
city: Cape Town
country: South Africa
state: Western Cape
city: Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Lugo
country: Spain
city: Madrid
country: Spain
city: Santander
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: