LUME-Lung 1: BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in 2nd Line Non Small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

Multicentre, Randomised, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral BIBF 1120 Plus Standard Docetaxel Therapy Compared to Placebo Plus Standard Docetaxel 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: NCT00805194
• Other study ID #: 1199.13
• Secondary ID: 2007-004803-36
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2008
• Est. completion date: November 13, 2017

Study information

• Verified date: November 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The present trial will be performed to evaluate whether BIBF 1120 in combination with standard therapy of docetaxel in patients with stage IIIB/IV or recurrent NSCLC is more effective as compared to placebo in combination with standard therapy of docetaxel. A secondary aim is to obtain safety information as well as information on quality of life of patients treated with BIBF 1120 in combination to standard therapy with docetaxel. In addition, blood will be collected for pharmacokinetic analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1314
• Est. completion date: November 13, 2017
• Est. primary completion date: November 2, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• male or female patient aged 18 years or older;

• histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of stage IIIB or IV or recurrent NSCLC;

• relapse or failure of one first line prior chemotherapy;

• at least one target tumour lesion that has not been irradiated within the past three months and that can accurately be measured ;

• life expectancy of at least three months;

• Eastern Cooperative Oncology group (ECOG) score of 0 or 1;

• patient has given written informed consent

Exclusion criteria:

• more than one prior chemotherapy regimen for advanced and/or metastatic or recurrent NSCLC;

• more than one chemotherapy treatment regimen (either neoadjuvant or adjuvant or neoadjuvant plus adjuvant) prior to first line chemotherapy;

• previous therapy with other VEGFR inhibitors (other than bevacizumab) or docetaxel for treatment of NSCLC;

• persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy;

• treatment with other investigational drugs or other anti-cancer therapy or treatment in another clinical trial within the past four weeks before start of - therapy or concomitantly with this trial ;

• radiotherapy (except extremities and brain) within the past three months prior to baseline imaging;

• active brain metastases or leptomeningeal disease;

• radiographic evidence of cavitary or necrotic tumours;

• centrally located tumours with radiographic evidence (CT or MRI) of local invasion of major blood vessels;

• history of clinically significant haemoptysis within the past 3 months;

• therapeutic anticoagulation (except low dose heparin) or antiplatelet therapy;

• history of major thrombotic or clinically relevant major bleeding event in the past 6 months;

• known inherited predisposition to bleeding or thrombosis;

• significant cardiovascular diseases ;

• inadequate safety laboratory parameters;

• significant weight loss (> 10 %) within the past 6 weeks;

• current peripheral neuropathy greater than CTCAE grade 2 except due to trauma;

• preexisting ascites and/or clinically significant pleural effusion;

• major injuries and/or surgery within the past ten days prior to randomisation with incomplete wound healing;

• serious infections requiring systemic antibiotic therapy;

• decompensated diabetes mellitus or other contraindication to high dose corticosteroid therapy;

• gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug;

• active or chronic hepatitis C and/or B infection;

• serious illness or concomitant non-oncological disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration;

• patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for at least twelve months after end of active therapy;

• pregnancy or breast feeding;

• psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule;

• patients unable to comply with the protocol;

• active alcohol or drug abuse;

• other malignancy within the past three years other than basal cell skin cancer, or carcinoma in situ of the cervix;

• any contraindications for therapy with docetaxel;

• history of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80);

• hypersensitivity to BIBF 1120 and/or the excipients of the trial drugs;

• hypersensitivity to contrast media

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• placebo plus docetaxel
placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel
• BIBF 1120 plus docetaxel
BIBF 1120 2 times daily along with standard therapy of docetaxel

Locations

Country	Name	City	State
Austria	LKH-Univ. Hospital Graz	Graz
Austria	KH St. Vinzenz, Zams, Int. Abtlg.	Kufstein
Austria	AKH d. Stadt Linz, Pulmologie	Linz
Belarus	Bobruisk Inter-distict	Bobruisk
Belarus	Brest Regional Clinical	Brest Region
Belarus	Gomel Regional Clinical	Gomel
Belarus	Public Health Inst. Minsk City Clinical Oncology Dispensary	Minsk
Belarus	Scientific Research Minsk	Minsk Region
Belarus	Mogilov Regional Oncological Dispensary	Mogilov
Belarus	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk
Belgium	Centre Hospitalier Universitaire de Liège	Liège
Belgium	Liège - HOSP CHR de la Citadelle	Liège
Bulgaria	Multiprofile Hospital for Active Treatment	Gabrovo
Bulgaria	Univ.Multiprofile Hospital "Dr. Georgy Stranski" EAD, Pleven	Pleven
Bulgaria	District Oncology Dispensary Plovdiv	Plovdiv
Bulgaria	Interdistrict Oncology Dispensary, Ruse	Ruse
Bulgaria	District Oncology Dispensary Shumen	Shumen
Bulgaria	Specialized Hospital for Active Treatment in Oncolcogy	Sofia
China	307 Hospital of PLA	Beijing
China	First Hospital of Jilin University	Changchun
China	Jilin Province Cancer Hospital	Changchun
China	West China Hospital	Chengdu
China	Southwest Hospital	Chongqing
China	First Affiliated Hospital of Dalian Medical University	Dalian
China	The Second Affiliated Hospital of Dalian Medical University	Dalian
China	Fujian Provincial Tumor Hospital	Fujian
China	Guangdong General Hospital	Guangzhou
China	Sun Yat-Sen University Cancer Center	Guangzhou
China	Sir Run Run Shaw Hospital	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	The Third Affiliated Hospital of Harbin Medical University	Harbin
China	Jiangsu Cancer Hospital	Nanjing
China	the 81th Hospital of PLA	Nanjing
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai Chest Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai
China	Tongji Hospital, Tongji University	Wuhan
China	Zhongshan Hospital Fudan University	Xuhui Area, Shanghai
Croatia	Clinical Hospital Centar Sestre Milosrdnice	Zagreb
Croatia	UHC Zagreb	Zagreb
Czechia	St. Anna Hospital, 2nd Internal Department	Brno
Czechia	University Hospital Brno	Brno
Czechia	District Hospital Liberec	Liberec
Czechia	Institut onkologie a rehabilitace Na Plesi s.r.o.	Nova Ves pod Plesi
Czechia	District Hospital Pribram, Oncology Centrum	Pribram
Denmark	Herlev Hospital	Herlev
Denmark	Odense Universitetshospital	Odense C
France	HOP Croix Rousse, Pneumo, Lyon	Lyon Cedex 4
France	INS Paoli-Calmettes	Marseille Cedex 9
France	HOP Lyon Sud	Pierre Bénite cedex
France	CHU de Rouen - Hôpital de Bois Guillaume	ROUEN cedex
France	HOP Nord Laënnec	Saint Herblain cedex
France	Oncology Institute of the Loire	Saint-Priest en Jarez
France	HOP Civil	Strasbourg cedex
France	Sainte Anne Training hospital for the armies	Toulon Cedex 09
Georgia	Amtel Hospital first Clinical LLC	Tbilisi
Georgia	Chemotherapy & Immunotherapy Clinic 'Medulla', Tbilisi	Tbilisi
Georgia	National Centre of Oncology	Tbilisi
Germany	Gemeinschaftspraxis Dr. Brudler / Dr. Heinrich, Augsburg	Augsburg
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Helios Klinikum Emil von Behring	Berlin
Germany	Universitätsklinikum Benjamin Franklin, Berlin	Berlin
Germany	Evangelische Lungenklinik Berlin	Berlin-Buch
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Klinikum Frankfurt Höchst GmbH	Frankfurt/Main
Germany	Krankenhaus Nordwest, Frankfurt	Frankfurt/Main
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Asklepios Fachkliniken München-Gauting	Gauting
Germany	Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH	Großhansdorf
Germany	Krankenhaus Martha-Maria Halle-Dölau gGmbH	Halle/Saale
Germany	Allgemeines Krankenhaus Harburg, 21075 Hamburg	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Klinikum Kassel GmbH	Kassel
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie, Köln	Köln
Germany	POIS Leipzig GbR	Leipzig
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinik, Löwenstein	Löwenstein
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel	Lübeck
Germany	Katholisches Klinikum St. Hildegardiskrankenhaus, Mainz	Mainz
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Klinikum rechts der Isar der Technischen Universität München	München
Germany	Städt. Krankenhaus, München-Bogenhausen	München
Germany	Universitätsklinik links der Isar, München, Ziemssenstr. 1	München
Germany	Pius-Hospital, Oldenburg	Oldenburg
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Helios Dr. Horst Schmidt Kliniken Wiesbaden	Wiesbaden
Germany	Evangelisches Krankenhaus, Witten	Witten
Greece	Athens Hospital of Chest Diseasea "SOTIRIA"	Athens
Greece	University Hospital of Heraklion, University Pulmonology Cl	Heraklio
Greece	Iaso General Hospital	Holargos, Athens
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloniki
Greece	Papageorgiou Hospital, 1st Cardiological Cl., Thessaloniki	Thessaloniki
India	Vedanta Institute of Medical Sciences	Ahmedabad
India	KIDWAI memoraial Institute of oncology	Bangalore
India	Rajalakshmi Multispeciality Hospital	Bangalore
India	Jawaharlal Nehru Cancer Hospital & Research Centre	Bhopal, M.P.
India	Apollo Hospital	Chennai
India	Bhagwan Mahaveer Cancer Hospital & Research Center, Jawahar	Jaipur
India	Birla Cancer Centre	Jaipur
India	SEAROC cancer center,S.K.soni Hospital	Jaipur, Rajasthan
India	B. P .Poddar Hospital & Medical Research Ltd.	Kolkata, West Bengal
India	Kasturba Medical College and Hospital	Mangalore
India	Tata Memorial Centre	Mumbai
India	Shatabdi Superspeciality Hospital	Nashik
India	Indraprastha Apollo Hospitals	New Delhi
India	Rajiv Gandhi Cancer Institute and Research Centre	New Delhi
India	Sir Gangaram Hospital	New Delhi
India	Jehangir Hospital Oncology Department	Pune, Maharahtra
India	Regional Cancer Center	Trivandrum, Kerala
India	City Cancer Centre, Cancer Hospital & Research	Vijayawada
India	King George Hospital	Visakhapatnam
Israel	E. Wolfson Medical Center, Holon 58100	Holon
Israel	Hadassah Medical Center, Ein-Karem	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	The Chaim Sheba Medical Center Tel Hashomer	Tel Hashomer
Israel	Sourasky Medical Center	Tel-Aviv
Israel	Assaf Harofe Medical Center	Zerifin
Italy	Az. Ospedaliere Umberto I di Ancona	Ancona
Italy	Centro di riferimento Oncologico	Aviano
Italy	Policlinico S. Orsola Malpighi	Bologna
Italy	Fond. Poliambulanza Istituto	Brescia
Italy	Azienda Ospedaliera Careggi	Firenze
Italy	Ospedale Civile	Ivrea (TO)
Italy	Istituto Scientifico Romagnolo	Meldola
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano
Italy	Azienda Sanitaria Ospedale S. Luigi Gonzaga	Orbassano
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	Ospedale S.Maria della Misericordia, AO di Perugia	Perugia
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	The Catholic University of Korea, Seoul St.Mary's Hospital	Seoul
Korea, Republic of	VHS Medical Center	Seoul
Lithuania	Hospital of Lithuanian Univ.of HealthSciences Kauno Klinikos	Kaunas
Lithuania	Siauliu ligonine, Siauliai	Siauliai
Lithuania	Vilniaus Universiteto	Vilnius
Poland	Pulmonology Center in Bydgoszcz	Bydgoszcz
Poland	Regional Complex Hospital	Elblag
Poland	Institute of Tuberculosis & Pulmonology, III. Dept., Olsztyn	Olsztyn
Poland	Mazowieckiego Centrum	Otwock
Poland	Greater PL Cent.Pulmo.&Thor.Surg.Eugenia&Janusz Zeyland	Poznan
Poland	Regional Specialist Hospital	Slupsk
Poland	Independent Public Hospital in Suwalki	Suwalki
Poland	Specialist Hospital, Szczecin-Zdunowo	Szczecin
Poland	Onco.Cent. - Instit. of Maria Sklodowskiej-Curie	Warszawa
Portugal	IPO Porto Francisco Gentil, EPE	Coimbra
Portugal	CHLN, EPE - Hospital de Santa Maria	Lisboa
Portugal	IPO Lisboa Francisco Gentil, EPE	Lisboa
Portugal	Centro Hospitalar São João,EPE	Porto
Portugal	IPO Porto Francisco Gentil, EPE	Porto
Portugal	CHS, EPE - Hospital de São Bernardo	Setúbal
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Romania	Baia Mare Emergency County Hospital	Baia Mare
Romania	Spitalul Clinic Judetean de Urgenta Brasov	Brasov
Romania	Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'	Bucuresti
Romania	Institutul Oncologic "Prof. Dr. Ion Chiricuta"	Cluj-Napoca
Romania	County Hospital "Dr. Alex Simionescu"	Hunedoara
Romania	Centrul de Oncologie Medicala	Iasi
Romania	Emergency Clinical County Hospital "Sf Spiridon", Iasi	Iasi
Romania	Onesti County Hospital	Onesti
Romania	Emergency County Hospital "Sf.loan cel Nou"	Suceava
Romania	Oncomed SRL	Timisoara
Russian Federation	SBIH of Arkhangelsk reg. "Arkhangelsk Clin. Onc. Dispensary"	Arkhangelsk
Russian Federation	GLPU Cheliabinsky	Chelyabinsk
Russian Federation	GUZ Irkutsk Regional Oncology Dispensary	Irkutsk
Russian Federation	St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"	Kazan
Russian Federation	RBIH "Kursk regional clinical oncology dispensary"	Kursk
Russian Federation	GUZ Regional Oncology Dispensary, Magnitogorsk	Magnitogorsk
Russian Federation	FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF	Moscow
Russian Federation	SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"	Pyatigorsk
Russian Federation	GUZ "Regional Clinical Oncology Dispensary"	Ryazan
Russian Federation	GUZ "Oncological Dispesary #2"	Sochi
Russian Federation	1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.	St. Petersburg
Russian Federation	FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF	St. Petersburg
Russian Federation	GUZ Leningradskaya Regional Clin. Hospital, St. Petersburg	St. Petersburg
Russian Federation	SPb SBIH "City Clinical Oncological Dispensary"	St. Petersburg
Russian Federation	GUZ Sverdlovsky Regional Oncology Dispensary	Yekaterinburg
Slovakia	Faculty Hospital Trnava	Trnava
South Africa	GVI oncology Medi Clinic	Cape Town
South Africa	Parklands Hospital	Durban
South Africa	Medical Oncology Centre of Rosebank	Johannesburg
South Africa	WCR CMJAH Clinical Trial Site	Johannesburg
South Africa	Langenhoven Drive Oncology Centre	Port Elizabeth
South Africa	Pretoria Academic Hospital	Pretoria
South Africa	Wilgers oncology	Pretoria
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario de Elche	Elche
Spain	Hospital Jerez de la Frontera	Jerez De La Frontera-Cádiz
Spain	Hospital La Princesa	Madrid
Spain	Hospital Quirónsalud Madrid	Pozuelo de Alarcon
Spain	Fundación Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Servicio de Oncologia Radiotherapica	Valencia
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital Baden AG	Baden
Ukraine	Chernigiv Regional Oncology Centre	Chernigiv
Ukraine	Bukovynsk State Medical University	Chernivtsi
Ukraine	Chmelnytskyi Oblasnnyi Oncologichnyi Tsentr	Chmelnytskyi
Ukraine	City Clinical Hospital #4, Dnipropetrovsk State Medical Academy	Dnipropetrovsk
Ukraine	Donetsk Regional Antitumor Centre	Donetsk
Ukraine	Kharkiv Medical Acadamy of Postgraduate education	Kharkiv
Ukraine	Kryvorizskyi regional communal clinical oncology centre	Kryvyi Rig
Ukraine	Odesa Regional Oncological Centre	Odesa
Ukraine	Ternopil regional communal clinical oncology centre	Ternopil
Ukraine	Uzhgorod National University, Oncology Centre	Uzhgorod
Ukraine	Vinnytsia Regional Clinical Oncological Dispensary	Vinnytsia
United Kingdom	Royal Bournemouth and Christchurch Hospital	Bournemouth
United Kingdom	Bristol Haematology & Onc. Ctr	Bristol
United Kingdom	Broomfield Hospital	Chelmsford
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	Poole Hospital	Poole

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belarus,  Belgium,  Bulgaria,  China,  Croatia,  Czechia,  Denmark,  France,  Georgia,  Germany,  Greece,  India,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

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 Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . 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 2 November 2010 (when 713 PFS events were observed)
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.; A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been.	From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )
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
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
Secondary	Objective Tumour 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.; As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.; This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013
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.; As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.; 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
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
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.; As per RECIST v1.0 for target lesions : Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.; This endpoint was analysed based on the central independent reviewer as well as the investigator.	From randomisation until cut-off date 15 February 2013
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
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 (squamous vs non-squamous), 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
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
Secondary	Quality of Life (QoL)	Quality of life (QoL) was measured by standardised questionnaires (Health Status Self-Assessment Questionnaire (EQ-5D), EORTC Quality of life questionnaire - Core 30 (EORTC QLQ-C30), Quality of life questionnaire - lung cancer module (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 (EORTC 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
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
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 42 months

External Links

•   Link