Lume Lung 2 : BIBF 1120 Plus Pemetrexed Compared to Placebo Plus Pemetrexed in 2nd Line Nonsquamous NSCLC

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00806819
• Other study ID #: 1199.14
• Secondary ID: 2008-002072-10
• Status: Completed
• Phase: Phase 3
• First received: December 10, 2008
• Last updated: January 22, 2016
• Start date: December 2008
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Ministry of HealthAustralia: Dept of Health and Ageing Therapeutic Goods AdminBosnia: Federal Ministry of HealthBrazil: National Health Surveillance AgencyCanada: Health CanadaChile: Instituto de Salud Pública de ChileColumbia: Instituto Nacional de Vigilancia de Medicamentos y AlimentosEcuador: Public Health MinistryGermany: Ministry of HealthHong Kong: Department of HealthHungary: National Institute of PharmacyIreland: Irish Medicines BoardKorea: Food and Drug AdministrationLatvia: State Agency of MedicinesMacedonia: Ministry of HealthMalaysia: Ministry of HealthMexico: Ministry of HealthMoldova: Ministry of HealthNetherlands: Ministry of Health, Welfare and SportNew Zealand: MedsafePanama: Commemorative Institute GORGAS of Studies of HealthPeru: Ministry of HealthPhilippines: Department of HealthPoland: Ministry of HealthRomania: Ministry of Public HealthSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSweden: The National Board of Health and WelfareTaiwan: Department of HealthThailand: Food and Drug AdministrationTurkey: Ministry of HealthUkraine: Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 718
• Est. completion date: December 2015
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Nintedanib (BIBF1120)
starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.
• Pemetrexed
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
• pemetrexed
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.
• B12
1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed
• dexamethasone (or corticosteroid equivalent)
4 mg PO bid the day before, the day of and the day after each pemetrexed infusion
• placebo
starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.
• dexamethasone (or corticosteroid equivalent)
4 mg PO bid the day before, the day of and the day after each pemetrexed infusion
• B12
1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed
• Folic Acid
400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.
• B12
1000 ug IM injection starting a week before first pemetrexed infusion and every 9 weeks thereafter until discontinuation of pemetrexed
• dexamethasone (or corticosteroid equivalent)
4 mg PO bid the day before, the day of and the day after each pemetrexed infusion
• Folic Acid
400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.
• placebo
starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.
• Folic Acid
400 ug once daily starting 1-2 weeks prior to the first dose of pemetrexed and continuing for at least 3 weeks after stopping pemetrexed.
• Nintedanib (BIBF1120)
starting dose of 200 mg bid taken daily except on the day of pemetrexed infusion . The dose can be reduced to 150 bid and then to 100 mg bid.
• Pemetrexed
500 mg/metre squared administered as an intravenous infusion over 10 minutes on Day 1 of each 21 day cycle.

Locations

Country	Name	City	State
Argentina	1199.14.2061 Boehringer Ingelheim Investigational Site	Bs. As. Codigo Buenos Aires
Argentina	1199.14.2052 Boehringer Ingelheim Investigational Site	Córdoba
Argentina	1199.14.2062 Boehringer Ingelheim Investigational Site	Pergamino
Argentina	1199.14.2067 Boehringer Ingelheim Investigational Site	Quilmes Buenos Aires
Argentina	1199.14.2068 Boehringer Ingelheim Investigational Site	Rosario, Santa Fe
Argentina	1199.14.2055 Boehringer Ingelheim Investigational Site	San Miguel de Tucuman
Argentina	1199.14.2056 Boehringer Ingelheim Investigational Site	San Miguel de Tucumán
Australia	1199.14.8053 Boehringer Ingelheim Investigational Site	Adelaide	South Australia
Australia	1199.14.8057 Boehringer Ingelheim Investigational Site	Brisbane	Queensland
Australia	1199.14.8054 Boehringer Ingelheim Investigational Site	Melbourne	Victoria
Australia	1199.14.8055 Boehringer Ingelheim Investigational Site	Perth	Western Australia
Australia	1199.14.8056 Boehringer Ingelheim Investigational Site	Sydney	New South Wales
Australia	1199.14.8059 Boehringer Ingelheim Investigational Site	Sydney
Australia	1199.14.8051 Boehringer Ingelheim Investigational Site	Toorak Gardens	South Australia
Bosnia and Herzegovina	1199.14.7151 Boehringer Ingelheim Investigational Site	Banja Luka
Bosnia and Herzegovina	1199.14.7152 Boehringer Ingelheim Investigational Site	Sarajevo
Brazil	1199.14.2161 Boehringer Ingelheim Investigational Site	Belo Horizonte
Brazil	1199.14.2183 Boehringer Ingelheim Investigational Site	Belo Horizonte
Brazil	1199.14.2176 Boehringer Ingelheim Investigational Site	Belo Horizonte,Minas Gerais
Brazil	1199.14.2185 Boehringer Ingelheim Investigational Site	Cachoeira do Itapemirim-ES
Brazil	1199.14.2182 Boehringer Ingelheim Investigational Site	Campinas SP
Brazil	1199.14.2156 Boehringer Ingelheim Investigational Site	Caxias do Sul
Brazil	1199.14.2165 Boehringer Ingelheim Investigational Site	Curitiba
Brazil	1199.14.2154 Boehringer Ingelheim Investigational Site	Florianopolis
Brazil	1199.14.2173 Boehringer Ingelheim Investigational Site	Goiania Goias
Brazil	1199.14.2157 Boehringer Ingelheim Investigational Site	Ijui
Brazil	1199.14.2158 Boehringer Ingelheim Investigational Site	Itajai
Brazil	1199.14.2159 Boehringer Ingelheim Investigational Site	Jau/SP
Brazil	1199.14.2177 Boehringer Ingelheim Investigational Site	Londrina, Parana
Brazil	1199.14.2171 Boehringer Ingelheim Investigational Site	Pelotas Rio Grande do Sul
Brazil	1199.14.2160 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	1199.14.2166 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	1199.14.2167 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	1199.14.2164 Boehringer Ingelheim Investigational Site	Rio de Janeiro
Brazil	1199.14.2151 Boehringer Ingelheim Investigational Site	Salvador Bahia
Brazil	1199.14.2178 Boehringer Ingelheim Investigational Site	Santo Andre
Brazil	1199.14.2170 Boehringer Ingelheim Investigational Site	Santo Andre, Sao Paulo
Brazil	1199.14.2155 Boehringer Ingelheim Investigational Site	Sao Paulo
Brazil	1199.14.2162 Boehringer Ingelheim Investigational Site	Sao Paulo
Brazil	1199.14.2180 Boehringer Ingelheim Investigational Site	Sao Paulo
Brazil	1199.14.2181 Boehringer Ingelheim Investigational Site	Sao Paulo
Brazil	1199.14.2168 Boehringer Ingelheim Investigational Site	Sao Paulo - SP
Brazil	1199.14.2172 Boehringer Ingelheim Investigational Site	Sorocaba Sao Paulo
Canada	1199.14.1553 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1199.14.1552 Boehringer Ingelheim Investigational Site	Quebec
Canada	1199.14.1554 Boehringer Ingelheim Investigational Site	Thunder Bay	Ontario
Canada	1199.14.1556 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1199.14.1557 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1199.14.1558 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Chile	1199.14.2259 Boehringer Ingelheim Investigational Site	Jardin del Mar, Renaca
Chile	1199.14.2254 Boehringer Ingelheim Investigational Site	Las Condes
Chile	1199.14.2251 Boehringer Ingelheim Investigational Site	Santiago
Chile	1199.14.2253 Boehringer Ingelheim Investigational Site	Santiago
Chile	1199.14.2256 Boehringer Ingelheim Investigational Site	Temuco
Colombia	1199.14.2352 Boehringer Ingelheim Investigational Site	Monteria, Cordoba
Ecuador	1199.14.3252 Boehringer Ingelheim Investigational Site	Cuenca
Ecuador	1199.14.3255 Boehringer Ingelheim Investigational Site	Quito
Germany	1199.14.4554 Boehringer Ingelheim Investigational Site	Augsburg
Germany	1199.14.4551 Boehringer Ingelheim Investigational Site	Berlin
Germany	1199.14.4555 Boehringer Ingelheim Investigational Site	Gauting
Germany	1199.14.4552 Boehringer Ingelheim Investigational Site	Halle (Saale)
Germany	1199.14.4567 Boehringer Ingelheim Investigational Site	Hemer
Germany	1199.14.4553 Boehringer Ingelheim Investigational Site	München
Hong Kong	1199.14.8251 Boehringer Ingelheim Investigational Site	Hong Kong
Hong Kong	1199.14.8252 Boehringer Ingelheim Investigational Site	Hong Kong
Hong Kong	1199.14.8253 Boehringer Ingelheim Investigational Site	Hong Kong
Hong Kong	1199.14.8255 Boehringer Ingelheim Investigational Site	Hong Kong
Hungary	1199.14.7251 Boehringer Ingelheim Investigational Site	Deszk
Hungary	1199.14.7252 Boehringer Ingelheim Investigational Site	Nyíregyháza
Hungary	1199.14.7253 Boehringer Ingelheim Investigational Site	Pécs
Ireland	1199.14.7351 Boehringer Ingelheim Investigational Site	Dublin 8
Korea, Republic of	1199.14.8557 Boehringer Ingelheim Investigational Site	Daegu
Korea, Republic of	1199.14.8563 Boehringer Ingelheim Investigational Site	Daegu
Korea, Republic of	1199.14.8562 Boehringer Ingelheim Investigational Site	Daejoen
Korea, Republic of	1199.14.8560 Boehringer Ingelheim Investigational Site	Gangdong-gu, Seoul
Korea, Republic of	1199.14.8551 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	1199.14.8552 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	1199.14.8556 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	1199.14.8565 Boehringer Ingelheim Investigational Site	Jeonbuk
Korea, Republic of	1199.14.8561 Boehringer Ingelheim Investigational Site	Seochogu, Seoul
Korea, Republic of	1199.14.8553 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.14.8554 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.14.8555 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.14.8558 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.14.8559 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1199.14.8564 Boehringer Ingelheim Investigational Site	Suwon
Latvia	1199.14.7451 Boehringer Ingelheim Investigational Site	Daugavpils
Latvia	1199.14.7452 Boehringer Ingelheim Investigational Site	Liepaja
Latvia	1199.14.7453 Boehringer Ingelheim Investigational Site	Riga
Macedonia, The Former Yugoslav R	1199.14.7552 Boehringer Ingelheim Investigational Site	Bitola
Macedonia, The Former Yugoslav R	1199.14.7553 Boehringer Ingelheim Investigational Site	Skopje
Macedonia, The Former Yugoslav R	1199.14.7554 Boehringer Ingelheim Investigational Site	Skopje
Malaysia	1199.14.8653 Boehringer Ingelheim Investigational Site	Georgetown
Malaysia	1199.14.8654 Boehringer Ingelheim Investigational Site	Kota Kinabalu
Malaysia	1199.14.8651 Boehringer Ingelheim Investigational Site	Kuala Lumpur
Malaysia	1199.14.8652 Boehringer Ingelheim Investigational Site	Kuching
Malaysia	1199.14.8655 Boehringer Ingelheim Investigational Site	Penang
Malaysia	1199.14.8656 Boehringer Ingelheim Investigational Site	Penang
Mexico	1199.14.2754 Boehringer Ingelheim Investigational Site	Chihuahua
Mexico	1199.14.2752 Boehringer Ingelheim Investigational Site	Morelia
Moldova, Republic of	1199.14.7651 Boehringer Ingelheim Investigational Site	Chisinau
Netherlands	1199.14.7752 Boehringer Ingelheim Investigational Site	Hertogenbosch
New Zealand	1199.14.8753 Boehringer Ingelheim Investigational Site	Auckland
New Zealand	1199.14.8751 Boehringer Ingelheim Investigational Site	Christchurch
New Zealand	1199.14.8754 Boehringer Ingelheim Investigational Site	Palmerston North
New Zealand	1199.14.8752 Boehringer Ingelheim Investigational Site	Wellington
Panama	1199.14.2852 Boehringer Ingelheim Investigational Site	Carrasquilla Panama
Panama	1199.14.2853 Boehringer Ingelheim Investigational Site	Panama
Peru	1199.14.2958 Boehringer Ingelheim Investigational Site	Arequipa
Peru	1199.14.2952 Boehringer Ingelheim Investigational Site	Cercado Arequipa
Peru	1199.14.2951 Boehringer Ingelheim Investigational Site	Lima
Peru	1199.14.2953 Boehringer Ingelheim Investigational Site	Lima
Peru	1199.14.2954 Boehringer Ingelheim Investigational Site	Lima
Peru	1199.14.2955 Boehringer Ingelheim Investigational Site	Lima
Peru	1199.14.2956 Boehringer Ingelheim Investigational Site	Lima
Peru	1199.14.2959 Boehringer Ingelheim Investigational Site	Lima
Philippines	1199.14.8854 Boehringer Ingelheim Investigational Site	Cebu
Philippines	1199.14.8856 Boehringer Ingelheim Investigational Site	Davao City
Philippines	1199.14.8853 Boehringer Ingelheim Investigational Site	Makati
Philippines	1199.14.8851 Boehringer Ingelheim Investigational Site	Quezon
Philippines	1199.14.8852 Boehringer Ingelheim Investigational Site	Quezon
Poland	1199.14.6651 Boehringer Ingelheim Investigational Site	Olsztyn
Romania	1199.14.6753 Boehringer Ingelheim Investigational Site	Baia Mare
Romania	1199.14.6752 Boehringer Ingelheim Investigational Site	Bucuresti
Romania	1199.14.6751 Boehringer Ingelheim Investigational Site	Cluj-Napoca
Romania	1199.14.6756 Boehringer Ingelheim Investigational Site	Iasi
Romania	1199.14.6754 Boehringer Ingelheim Investigational Site	Onesti
Romania	1199.14.6755 Boehringer Ingelheim Investigational Site	Timisoara
Serbia	1199.14.7851 Boehringer Ingelheim Investigational Site	Belgrade
Serbia	1199.14.7852 Boehringer Ingelheim Investigational Site	Belgrade
Serbia	1199.14.7853 Boehringer Ingelheim Investigational Site	Belgrade
Serbia	1199.14.7855 Boehringer Ingelheim Investigational Site	Nis
Serbia	1199.14.7854 Boehringer Ingelheim Investigational Site	Sremska Kamenica
Sweden	1199.14.7052 Boehringer Ingelheim Investigational Site	Gävle
Sweden	1199.14.7054 Boehringer Ingelheim Investigational Site	Stockholm
Sweden	1199.14.7055 Boehringer Ingelheim Investigational Site	Umeå
Sweden	1199.14.7053 Boehringer Ingelheim Investigational Site	Uppsala
Taiwan	1199.14.9057 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1199.14.9054 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1199.14.9055 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1199.14.9062 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1199.14.9056 Boehringer Ingelheim Investigational Site	Tainan
Taiwan	1199.14.9053 Boehringer Ingelheim Investigational Site	Tainan City
Taiwan	1199.14.9051 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1199.14.9052 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1199.14.9061 Boehringer Ingelheim Investigational Site	Taipei
Thailand	1199.14.9152 Boehringer Ingelheim Investigational Site	Bangkok
Thailand	1199.14.9153 Boehringer Ingelheim Investigational Site	Bangkok
Thailand	1199.14.9154 Boehringer Ingelheim Investigational Site	Chiang Mai
Turkey	1199.14.7951 Boehringer Ingelheim Investigational Site	Ankara
Turkey	1199.14.7963 Boehringer Ingelheim Investigational Site	Ankara
Turkey	1199.14.7956 Boehringer Ingelheim Investigational Site	Antalya
Turkey	1199.14.7961 Boehringer Ingelheim Investigational Site	Aydin
Turkey	1199.14.7953 Boehringer Ingelheim Investigational Site	Balcali-Adana
Turkey	1199.14.7957 Boehringer Ingelheim Investigational Site	Diyarbakir
Turkey	1199.14.7958 Boehringer Ingelheim Investigational Site	Gaziantep
Turkey	1199.14.7960 Boehringer Ingelheim Investigational Site	Kocaeli
Ukraine	1199.14.6955 Boehringer Ingelheim Investigational Site	Chernigiv
Ukraine	1199.14.6953 Boehringer Ingelheim Investigational Site	Dnipropetrovks
Ukraine	1199.14.6951 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	1199.14.6958 Boehringer Ingelheim Investigational Site	Uzhgorod
Ukraine	1199.14.6956 Boehringer Ingelheim Investigational Site	Vinnytsia
United States	1199.14.1096 Boehringer Ingelheim Investigational Site	Amarillo	Texas
United States	1199.14.1254 Boehringer Ingelheim Investigational Site	Asheville	North Carolina
United States	1199.14.1079 Boehringer Ingelheim Investigational Site	Ashland	Kentucky
United States	1199.14.1199 Boehringer Ingelheim Investigational Site	Aventura	Florida
United States	1199.14.1194 Boehringer Ingelheim Investigational Site	Boynton Beach	Florida
United States	1199.14.1051 Boehringer Ingelheim Investigational Site	Burlington	Massachusetts
United States	1199.14.1174 Boehringer Ingelheim Investigational Site	Canton	Ohio
United States	1199.14.1092 Boehringer Ingelheim Investigational Site	Downy	California
United States	1199.14.1165 Boehringer Ingelheim Investigational Site	Dunkirk	New York
United States	1199.14.1179 Boehringer Ingelheim Investigational Site	Ephrata	Pennsylvania
United States	1199.14.1094 Boehringer Ingelheim Investigational Site	Farmington	New Mexico
United States	1199.14.1093 Boehringer Ingelheim Investigational Site	Fountain Valley	California
United States	1199.14.1164 Boehringer Ingelheim Investigational Site	Fullerton	California
United States	1199.14.1188 Boehringer Ingelheim Investigational Site	Galesburg	Illinois
United States	1199.14.1056 Boehringer Ingelheim Investigational Site	Germantown	Tennessee
United States	1199.14.1099 Boehringer Ingelheim Investigational Site	Goshen	New York
United States	1199.14.1086 Boehringer Ingelheim Investigational Site	Grand Island	Nebraska
United States	1199.14.1152 Boehringer Ingelheim Investigational Site	Indianapolis	Indiana
United States	1199.14.1196 Boehringer Ingelheim Investigational Site	Indianapolis	Indiana
United States	1199.14.1160 Boehringer Ingelheim Investigational Site	Jacksonville	Florida
United States	1199.14.1256 Boehringer Ingelheim Investigational Site	Lake Success	New York
United States	1199.14.1065 Boehringer Ingelheim Investigational Site	Langhorne	Pennsylvania
United States	1199.14.1181 Boehringer Ingelheim Investigational Site	Long Beach	California
United States	1199.14.1172 Boehringer Ingelheim Investigational Site	Louisville	Kentucky
United States	1199.14.1186 Boehringer Ingelheim Investigational Site	Madison	Wisconsin
United States	1199.14.1080 Boehringer Ingelheim Investigational Site	Meriden	Connecticut
United States	1199.14.1061 Boehringer Ingelheim Investigational Site	Miami	Florida
United States	1199.14.1088 Boehringer Ingelheim Investigational Site	Milwaukee	Wisconsin
United States	1199.14.1058 Boehringer Ingelheim Investigational Site	New Albany	Indiana
United States	1199.14.1057 Boehringer Ingelheim Investigational Site	New Port Richey	Florida
United States	1199.14.1151 Boehringer Ingelheim Investigational Site	Nyack	New York
United States	1199.14.1169 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania
United States	1199.14.1054 Boehringer Ingelheim Investigational Site	Port St. Lucie	Florida
United States	1199.14.1071 Boehringer Ingelheim Investigational Site	Sandusky	Ohio
United States	1199.14.1158 Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	1199.14.1261 Boehringer Ingelheim Investigational Site	Skokie	Illinois
United States	1199.14.1259 Boehringer Ingelheim Investigational Site	Spokane	Washington
United States	1199.14.1182 Boehringer Ingelheim Investigational Site	Springfield	Massachusetts
United States	1199.14.1098 Boehringer Ingelheim Investigational Site	St. Louis park	Minnesota
United States	1199.14.1055 Boehringer Ingelheim Investigational Site	Stuart	Florida
United States	1199.14.1097 Boehringer Ingelheim Investigational Site	Witchita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bosnia and Herzegovina,  Brazil,  Canada,  Chile,  Colombia,  Ecuador,  Germany,  Hong Kong,  Hungary,  Ireland,  Korea, Republic of,  Latvia,  Macedonia, The Former Yugoslav Republic of,  Malaysia,  Mexico,  Moldova, Republic of,  Netherlands,  New Zealand,  Panama,  Peru,  Philippines,  Poland,  Romania,  Serbia,  Sweden,  Taiwan,  Thailand,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) as Assessed by Central Independent Review	Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria. Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier).; Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 9 July 2012	No
Secondary	Overall Survival (Key Secondary Endpoint)	Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 15 February 2013	No
Secondary	Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review	Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 15 February 2013	No
Secondary	Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator	Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 15 February 2013	No
Secondary	Objective Tumor Response	Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0. This endpoint was analysed based on the central independent reviewer as well as the investigator	From randomisation until cut-off date 15 February 2013	No
Secondary	Duration of Confirmed Objective Tumour Response	The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.; This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013	No
Secondary	Time to Confirmed Objective Tumour Response	Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.; This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013	No
Secondary	Disease Control	Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.; This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013	No
Secondary	Duration of Disease Control	The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.; This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013	No
Secondary	Change From Baseline in Tumour Size	Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion. Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (adenocarcinoma vs. non-adenocarcinoma), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no) This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013	No
Secondary	Clinical Improvement.	Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.; Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 15 February 2013	No
Secondary	Quality of Life (QoL)	QoL was measured by standardised questionnaires (EQ-5D, EORTC QLQ-C30, EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items. The following were the main points of interest: Time to deterioration of cough (QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19). Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.; Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.	From randomisation until cut-off date 15 February 2013	No
Secondary	Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide	Geometric mean of dose normalised predose plasma concentration (Cpre,ss,norm) of nintedanib and of its metabolites BIBF 1202 and BIBF 1202 glucuronide evaluated at steady state based on course 2 and 3. If only one value was available and valid, then this value was used for calculation of Cpre,ss,norm.	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	No
Secondary	Incidence and Intensity of Adverse Events	Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.; Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint.	From the first drug administration until 28 days after the last drug administration, up to 36 months	No