Clinical trial NCT00863746: A 3rd/4th Line Placebo-controlled Trial of Sorafenib in Patients With Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC).
Official title: A Phase III, Multi-center, Placebo-Controlled Trial of Sorafenib (BAY43-9006) in Patients With Relapsed or Refractory Advanced Predominantly Non Squamous Non-Small Cell Lung Cancer (NSCLC) After 2 or 3 Previous Treatment Regimens for Advanced Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma
Non-Small-Cell Lung
Keywords: Non-Small Cell Lung Cancer (NSCLC)
Sorafenib
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-03-18
Enrollment: 703
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: The purpose of the study is to see if sorafenib plus best supportive care (i.e. in addition to the non-cancer treatments patients would normally receive) is an effective treatment for lung cancer compared to best supportive care alone. The safety and tolerability of the two treatment groups will also be compared. The goal of the study is to test the ability of sorafenib to improve survival compared to best supportive care alone.

Detailed description: Acronyms used in Adverse Events section: Disseminated intravascular coagulation (DIC), International normalized ratio (INR), Atrioventricular (AV), Gastrointestinal (GI), Not otherwise specified (NOS), Common Terminology Criteria for Adverse Events (CTCAE), Absolute neutrophil count (ANC), Central nervous system (CNS), Acute respiratory distress syndrome (ARDS), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST).

Eligibility criteria: Inclusion Criteria:

* Ability to understand and willingness to sign a written Informed Consent
* Advanced relapsed or refractory predominantly non squamous NSCLC. The diagnosis must have been confirmed cyto-/ histologically
* Patients must have measurable or non-measurable disease
* At least two but not more than three prior standard treatment regimens for NSCLC
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Male or female subjects \>/= 18 years of age (\>/=20 for Japan) at the time of Informed Consent
* Life expectancy of at least 12 weeks
* Ability to swallow oral medication
* Both men and women using adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of the study drug:

  * Haemoglobin \> 9.0 g/dl
  * Absolute neutrophil count (ANC) \>1,500/mm3
  * Platelet count \>/= 100,000/µl
  * Total bilirubin \</=1.5 x the upper limit of normal
  * Alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (\</= 5 x upper limit of normal in patients with liver metastases) Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (\</= 5 x upper limit of normal in patients with liver metastases)
  * Alkaline phosphatase \< 4 x upper limit of normal (\</= 5 x upper limit of normal in patients with liver metastases)
  * Prothrombin Time (PT)-International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) \< 1.5 x upper limit of normal
  * Serum creatinine \< 1.5 x upper limit of normal
  * Calculated creatinine clearance of \>/= 50 mL/min

Exclusion Criteria:

* NSCLC patients with predominantly squamous cell carcinoma histology

Excluded medical conditions:

* History of cardiac disease: Congestive heart failure, Active coronary artery disease (CAD), Cardiac arrhythmias (\>Grade 2 NCI-CTCAE \[National Cancer Institute-Common Terminology Criteria for Adverse Events\] vers. 3.0)
* Uncontrolled hypertension despite two anti-hypertensive medications
* History of Human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* History of organ allograft
* Active clinically serious infections (\> grade 2 NCI-CTCAE vers. 3.0)
* Patients with seizure disorder requiring medication
* Patients with evidence or history of bleeding diathesis or coagulopathy
* Patients undergoing renal dialysis
* Pulmonary hemorrhage/ bleeding event \>/= CTCAE grade 2 within four weeks prior to the first dose of the study drug
* Any other hemorrhage/ bleeding event \>/= CTCAE grade 3 within four weeks prior to the first dose of the study drug
* Thrombotic or embolic venous or arterial events such as cerebrovascular accident
* Pregnant or breast-feeding women.
* Any condition which could affect the absorption or pharmacokinetics of the study drug
* Prior treatment with other Vascular Endothelial Growth Factor (VEGF) (R) inhibitors, including compounds that impact vascularity (i.e. sunitinib, thalidomide, vandetanib, vascular disrupting agents \[VDA\], VEGF-trap and other experimental agents of this class). Only bevacizumab (Avastin) is permitted.

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization of the first subject until 36 months later
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From randomization of the first subject until 36 months later assessed every 6 weeks
measure: Disease Control
timeFrame: From randomization of the first subject until 36 months later assessed every 6 weeks
measure: Objective Tumor Response
timeFrame: From randomization of the first subject until 36 months later assessed every 6 weeks
measure: Time to Progression
timeFrame: From randomization of the first subject until 36 months later assessed every 6 weeks
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) - Global Health Status
timeFrame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Coughing Subscale
timeFrame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
measure: Mean Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) - Dyspnea
timeFrame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
measure: Mean Change From Baseline in EuroQol-5D (EQ-5D) - Index Score
timeFrame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
measure: Mean Change From Baseline in EuroQol-5D (EQ-5D) - VAS Score
timeFrame: Baseline and up to End of treatment (up to Cycle 41, 21 days per cycle)
Other outcomes:
Locations:
city: Fayetteville
country: United States
state: Arkansas
city: Stanford
country: United States
state: California
city: Philadelphia
country: United States
state: Pennsylvania
city: Ramos Mejía
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Rosario
country: Argentina
state: Santa Fe
city: Rosario
country: Argentina
state: Santa Fe
city: Córdoba
country: Argentina
city: Córdoba
country: Argentina
city: Santa Fé
country: Argentina
city: Graz
country: Austria
city: Linz
country: Austria
city: Wien
country: Austria
city: Antwerpen
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Charleroi
country: Belgium
city: Genk
country: Belgium
city: Brasilia
country: Brazil
state: Distrito Federal
city: Belo Horizonte
country: Brazil
state: Minas Gerais
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: Santo André
country: Brazil
state: Sao Paulo
city: São José dos Campos
country: Brazil
state: Sao Paulo
city: São Paulo
country: Brazil
state: Sao Paulo
city: Sao Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Varna
country: Bulgaria
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: Chengdu
country: China
state: Sichuan
city: Hangzhou
country: China
state: Zhejiang
city: Hangzhou
country: China
state: Zhejiang
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Beijing
country: China
city: Guangzhou
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Caen
country: France
city: Dijon
country: France
city: La Roche Sur Yon Cedex
country: France
city: La Tronche
country: France
city: Lille
country: France
city: Lyon Cedex
country: France
city: Saint Herblain
country: France
city: Tours
country: France
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Karlsruhe
country: Germany
state: Baden-Württemberg
city: Mannheim
country: Germany
state: Baden-Württemberg
city: Ulm
country: Germany
state: Baden-Württemberg
city: Gauting
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Kassel
country: Germany
state: Hessen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Großhansdorf
country: Germany
state: Schleswig-Holstein
city: Bad Berka
country: Germany
state: Thüringen
city: Hamburg
country: Germany
city: Athens
country: Greece
city: Heraklion
country: Greece
city: Thessaloniki
country: Greece
city: Shatin
country: Hong Kong
state: N.T
city: Hongkong
country: Hong Kong
city: Kowloon
country: Hong Kong
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Edeleny
country: Hungary
city: Farkasgyepu
country: Hungary
city: Torokbalint
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Mumbai
country: India
state: Maharashtra
city: Pune
country: India
state: Maharashtra
city: Kerala
country: India
city: Bandung
country: Indonesia
city: Jakarta
country: Indonesia
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petach Tikva
country: Israel
city: Zrifin
country: Israel
city: Rozzano
country: Italy
state: Milano
city: Monza
country: Italy
state: Monza-Brianza
city: Orbassano
country: Italy
state: Torino
city: Avellino
country: Italy
city: Genova
country: Italy
city: Livorno
country: Italy
city: Parma
country: Italy
city: Perugia
country: Italy
city: Roma
country: Italy
city: Nagoya
country: Japan
state: Aichi
city: Kashiwa
country: Japan
state: Chiba
city: Akashi
country: Japan
state: Hyogo
city: Osakasayama
country: Japan
state: Osaka
city: Sakai
country: Japan
state: Osaka
city: Itabashi-ku
country: Japan
state: Tokyo
city: Koto-ku
country: Japan
state: Tokyo
city: Fukuoka
country: Japan
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
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: Amsterdam
country: Netherlands
city: Harderwijk
country: Netherlands
city: Heerlen
country: Netherlands
city: Helmond
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Zwolle
country: Netherlands
city: Lahore
country: Pakistan
state: Punjab
city: Karachi
country: Pakistan
state: Sindh
city: Callao
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: San Borja
country: Peru
city: Cebu City
country: Philippines
city: Manila
country: Philippines
city: Metro Manila
country: Philippines
city: Quezon City
country: Philippines
city: Kielce
country: Poland
city: Krakow
country: Poland
city: Olsztyn
country: Poland
city: Rzeszow
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Kazan
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Port Elizabeth
country: South Africa
state: Eastern Cape
city: Johannesburg
country: South Africa
state: Gauteng
city: Prietoria
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: Kwazulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: Cruces/Barakaldo
country: Spain
state: Bilbao
city: Orense
country: Spain
state: Ourense
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Lleida
country: Spain
city: Lugo
country: Spain
city: Madrid
country: Spain
city: Málaga
country: Spain
city: Sevilla
country: Spain
city: Zamora
country: Spain
city: Falun
country: Sweden
city: Göteborg
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Songkhla
country: Thailand
city: Ankara
country: Turkey
city: Instanbul
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kocaeli
country: Turkey
city: Bristol
country: United Kingdom
state: Avon
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Greater Manchester
country: United Kingdom
state: Manchester
city: Sutton
country: United Kingdom
state: Surrey
city: Leeds
country: United Kingdom
state: West Yorkshire
city: Aberdeen
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: