Clinical trial NCT00806819: Lume Lung 2 : BIBF 1120 Plus Pemetrexed Compared to Placebo Plus Pemetrexed in 2nd Line Nonsquamous NSCLC
Official title: Multicenter, Randomized, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral BIBF 1120 Plus Standard Pemetrexed Therapy Compared to Placebo Plus Standard Pemetrexed Therapy in Patients With Stage IIIB/IV or Recurrent Non Small Cell Lung Cancer After Failure of First Line Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-12-11
Enrollment: 718
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 trial will be performed to evaluate if BIBF 1120 in combination with standard pemetrexed therapy is more effective than placebo (inactive capsule) plus standard pemetrexed therapy in patients with stage IIIB, IV or recurrent NSCLC. Safety information about BIBF1120/pemetrexed will be obtained.


Eligibility criteria: Inclusion criteria:

1. Male or female patient aged 18 years or older.
2. Histologically or cytologically confirmed Stage IIIB, IV (according to AJCC) or recurrent non small cell lung cancer (NSCLC) (non squamous histologies)
3. Relapse or failure of one first line chemotherapy (in the case of recurrent disease one additional prior regimen is allowed for adjuvant, neoadjuvant or neoadjuvant plus adjuvant therapy).
4. At least one target tumor lesion that has not been irradiated within the past three months and that can accurately be measured by magnetic resonance imaging (MRI) or computed tomography (CT) in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT.
5. Life expectancy of at least three months.
6. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
7. Patient has given written informed consent which must be consistent with the International Conference on Harmonization, Good Clinical Practice (ICH-GCP) and local legislation.

Exclusion criteria:

1. Previous therapy with other vascular endothelial growth factor (VEGF) inhibitors (other than bevacizumab) or pemetrexed for treatment of NSCLC
2. Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial
3. Chemotherapy, hormone therapy, immunotherapy with monoclonal antibodies, treatment with tyrosine kinase inhibitors, or radiotherapy (except for treatment of extremities) within the past four weeks prior to treatment with the trial drug, i.e., the minimum time elapsed since the last anticancer therapy and the first administration of BIBF 1120 must be four weeks
4. Inability to stop intake of NSAIDS (non steroidal anti inflammatory drugs) for several days
5. Active brain metastases (e.g. stable for \<4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants). Dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomisation)
6. Radiographic evidence of cavitary or necrotic tumors
7. Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels
8. History of clinically significant haemoptysis within the past 3 months
9. Therapeutic anticoagulation
10. History of major thrombotic or clinically relevant major bleeding event in the past 6 months
11. Significant cardiovascular diseases (i.e., hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months,
12. Inadequate kidney, liver, blood clotting function
13. Inadequate blood count
14. Significant weight loss (\> 10 %) within the past 6 weeks prior to treatment in the present trial
15. Current peripheral neuropathy greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 except due to trauma
16. Pre-existing ascites (abdominal fluid collection) and/or clinically significant pleural effusion ( fluid collection between the lung and chest wall)
17. Major injuries and/or surgery within the past ten days prior to start of study drug
18. Incomplete wound healing
19. Active or chronic hepatitis C and/or B infection Additional exclusion criteria apply

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Central Independent Review
timeFrame: From randomisation until cut-off date 9 July 2012
Secondary outcomes:
measure: Overall Survival (Key Secondary Endpoint)
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Objective Tumor Response
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Duration of Confirmed Objective Tumour Response
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Time to Confirmed Objective Tumour Response
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Disease Control
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Duration of Disease Control
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Change From Baseline in Tumour Size
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Clinical Improvement.
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Quality of Life (QoL)
timeFrame: From randomisation until data cut-off (15 February 2013), Up to 30 months
measure: Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide
timeFrame: Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3
measure: Incidence and Intensity of Adverse Events
timeFrame: From the first drug administration until 28 days after the last drug administration, up to 36 months
Other outcomes:
Locations:
city: Downy
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Fountain Valley
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Fullerton
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Long Beach
country: United States
facility: Boehringer Ingelheim Investigational Site
state: California
city: Meriden
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Connecticut
city: Aventura
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Boynton Beach
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Miami
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Port St. Lucie
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Stuart
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Florida
city: Galesburg
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Illinois
city: Skokie
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Illinois
city: Indianapolis
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Indiana
city: New Albany
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Indiana
city: Witchita
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Kansas
city: Ashland
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Kentucky
city: Burlington
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Massachusetts
city: St. Louis park
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Minnesota
city: Grand Island
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Nebraska
city: Farmington
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New Mexico
city: Dunkirk
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Goshen
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Lake Success
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Nyack
country: United States
facility: Boehringer Ingelheim Investigational Site
state: New York
city: Asheville
country: United States
facility: Boehringer Ingelheim Investigational Site
state: North Carolina
city: Canton
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Ohio
city: Sandusky
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Ohio
city: Ephrata
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Langhorne
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Germantown
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Texas
city: Seattle
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Washington
city: Spokane
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Washington
city: Madison
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Milwaukee
country: United States
facility: Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Bs. As. Codigo Buenos Aires
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Córdoba
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Pergamino
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Quilmes Buenos Aires
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Rosario, Santa Fe
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: San Miguel de Tucuman
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: San Miguel de Tucumán
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Sydney
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: New South Wales
city: Brisbane
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Queensland
city: Adelaide
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: South Australia
city: Toorak Gardens
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: South Australia
city: Melbourne
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Victoria
city: Perth
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Western Australia
city: Sydney
country: Australia
facility: Boehringer Ingelheim Investigational Site
city: Banja Luka
country: Bosnia and Herzegovina
facility: Boehringer Ingelheim Investigational Site
city: Sarajevo
country: Bosnia and Herzegovina
facility: Boehringer Ingelheim Investigational Site
city: Belo Horizonte,Minas Gerais
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Belo Horizonte
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Cachoeira do Itapemirim-ES
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Campinas SP
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Caxias do Sul
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Curitiba
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Florianopolis
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Goiania Goias
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Ijui
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Itajai
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Jau/SP
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Londrina, Parana
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Pelotas Rio Grande do Sul
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Rio de Janeiro
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Salvador Bahia
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Santo Andre, Sao Paulo
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Santo Andre
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Sao Paulo - SP
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Sorocaba Sao Paulo
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Thunder Bay
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Boehringer Ingelheim Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: Boehringer Ingelheim Investigational Site
city: Jardin del Mar, Renaca
country: Chile
facility: Boehringer Ingelheim Investigational Site
city: Las Condes
country: Chile
facility: Boehringer Ingelheim Investigational Site
city: Santiago
country: Chile
facility: Boehringer Ingelheim Investigational Site
city: Temuco
country: Chile
facility: Boehringer Ingelheim Investigational Site
city: Monteria, Cordoba
country: Colombia
facility: Boehringer Ingelheim Investigational Site
city: Cuenca
country: Ecuador
facility: Boehringer Ingelheim Investigational Site
city: Quito
country: Ecuador
facility: Boehringer Ingelheim Investigational Site
city: Augsburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Gauting
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Halle (Saale)
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hemer
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hong Kong
country: Hong Kong
facility: Boehringer Ingelheim Investigational Site
city: Deszk
country: Hungary
facility: Boehringer Ingelheim Investigational Site
city: Nyíregyháza
country: Hungary
facility: Boehringer Ingelheim Investigational Site
city: Pécs
country: Hungary
facility: Boehringer Ingelheim Investigational Site
city: Dublin 8
country: Ireland
facility: Boehringer Ingelheim Investigational Site
city: Daegu
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Daejoen
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Gangdong-gu, Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Jeonbuk
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seochogu, Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Suwon
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Daugavpils
country: Latvia
facility: Boehringer Ingelheim Investigational Site
city: Liepaja
country: Latvia
facility: Boehringer Ingelheim Investigational Site
city: Riga
country: Latvia
facility: Boehringer Ingelheim Investigational Site
city: Bitola
country: Macedonia, The Former Yugoslav Republic of
facility: Boehringer Ingelheim Investigational Site
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Boehringer Ingelheim Investigational Site
city: Georgetown
country: Malaysia
facility: Boehringer Ingelheim Investigational Site
city: Kota Kinabalu
country: Malaysia
facility: Boehringer Ingelheim Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Boehringer Ingelheim Investigational Site
city: Kuching
country: Malaysia
facility: Boehringer Ingelheim Investigational Site
city: Penang
country: Malaysia
facility: Boehringer Ingelheim Investigational Site
city: Chihuahua
country: Mexico
facility: Boehringer Ingelheim Investigational Site
city: Morelia
country: Mexico
facility: Boehringer Ingelheim Investigational Site
city: Chisinau
country: Moldova, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Hertogenbosch
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Auckland
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Christchurch
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Palmerston North
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Wellington
country: New Zealand
facility: Boehringer Ingelheim Investigational Site
city: Carrasquilla Panama
country: Panama
facility: Boehringer Ingelheim Investigational Site
city: Panama
country: Panama
facility: Boehringer Ingelheim Investigational Site
city: Arequipa
country: Peru
facility: Boehringer Ingelheim Investigational Site
city: Cercado Arequipa
country: Peru
facility: Boehringer Ingelheim Investigational Site
city: Lima
country: Peru
facility: Boehringer Ingelheim Investigational Site
city: Cebu
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: Davao City
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: Makati
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: Quezon
country: Philippines
facility: Boehringer Ingelheim Investigational Site
city: Olsztyn
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Baia Mare
country: Romania
facility: Boehringer Ingelheim Investigational Site
city: Bucuresti
country: Romania
facility: Boehringer Ingelheim Investigational Site
city: Cluj-Napoca
country: Romania
facility: Boehringer Ingelheim Investigational Site
city: Iasi
country: Romania
facility: Boehringer Ingelheim Investigational Site
city: Onesti
country: Romania
facility: Boehringer Ingelheim Investigational Site
city: Timisoara
country: Romania
facility: Boehringer Ingelheim Investigational Site
city: Belgrade
country: Serbia
facility: Boehringer Ingelheim Investigational Site
city: Nis
country: Serbia
facility: Boehringer Ingelheim Investigational Site
city: Sremska Kamenica
country: Serbia
facility: Boehringer Ingelheim Investigational Site
city: Gävle
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Umeå
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Tainan City
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Tainan
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Bangkok
country: Thailand
facility: Boehringer Ingelheim Investigational Site
city: Chiang Mai
country: Thailand
facility: Boehringer Ingelheim Investigational Site
city: Ankara
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Antalya
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Aydin
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Balcali-Adana
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Diyarbakir
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Gaziantep
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Kocaeli
country: Turkey
facility: Boehringer Ingelheim Investigational Site
city: Chernigiv
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Dnipropetrovks
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Uzhgorod
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Vinnytsia
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Lesaffre E, Edelman MJ, Hanna NH, Park K, Thatcher N, Willemsen S, Gaschler-Markefski B, Kaiser R, Manegold C. Statistical controversies in clinical research: futility analyses in oncology-lessons on potential pitfalls from a randomized controlled trial. Ann Oncol. 2017 Jul 1;28(7):1419-1426. doi: 10.1093/annonc/mdx042.