LUME-Lung 1: BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in 2nd Line Non Small Cell Lung Cancer
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
2 other identifiers
interventional
1,314
26 countries
208
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2008
Longer than P75 for phase_3
208 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 3, 2008
CompletedFirst Submitted
Initial submission to the registry
December 8, 2008
CompletedFirst Posted
Study publicly available on registry
December 9, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 2, 2010
CompletedResults Posted
Study results publicly available
December 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
November 13, 2017
CompletedDecember 5, 2018
November 1, 2018
1.9 years
December 8, 2008
November 14, 2014
November 9, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (13)
Overall Survival (Key Secondary Endpoint)
From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review
From randomisation until cut-off date 15 February 2013
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator
From randomisation until cut-off date 15 February 2013
Objective Tumour Response
From randomisation until cut-off date 15 February 2013
Duration of Confirmed Objective Tumour Response
From randomisation until cut-off date 15 February 2013
- +8 more secondary outcomes
Study Arms (2)
BIBF 1120 plus docetaxel
EXPERIMENTALBIBF 1120 2 times daily along with standard therapy of docetaxel
Placebo plus docetaxel
PLACEBO COMPARATORPlacebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel
Interventions
placebo matching BIBF 1120 2 times daily along with standard therapy of docetaxel
BIBF 1120 2 times daily along with standard therapy of docetaxel
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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;
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (210)
LKH-Univ. Hospital Graz
Graz, 8036, Austria
KH St. Vinzenz, Zams, Int. Abtlg.
Kufstein, 6330, Austria
AKH d. Stadt Linz, Pulmologie
Linz, 4020, Austria
Bobruisk Inter-distict
Babruysk, 213825, Belarus
Brest Regional Clinical
Brest Region, 224027, Belarus
Gomel Regional Clinical
Homyel, 246012, Belarus
Public Health Inst. Minsk City Clinical Oncology Dispensary
Minsk, 220013, Belarus
Scientific Research Minsk
Minsk Region, 223040, Belarus
Mogilov Regional Oncological Dispensary
Mogilev, 212018, Belarus
Vitebsk Regional Clinical Oncology Dispensary
Vitebsk, 210603, Belarus
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
Liège - HOSP CHR de la Citadelle
Liège, 4000, Belgium
Multiprofile Hospital for Active Treatment
Gabrovo, 5300, Bulgaria
Univ.Multiprofile Hospital "Dr. Georgy Stranski" EAD, Pleven
Pleven, 5800, Bulgaria
District Oncology Dispensary Plovdiv
Plovdiv, 4004, Bulgaria
Interdistrict Oncology Dispensary, Ruse
Rousse, 7002, Bulgaria
District Oncology Dispensary Shumen
Shumen, 9700, Bulgaria
Specialized Hospital for Active Treatment in Oncolcogy
Sofia, 1756, Bulgaria
307 Hospital of PLA
Beijing, 100071, China
Jilin Province Cancer Hospital
Changchun, 130012, China
First Hospital of Jilin University
Changchun, 130021, China
West China Hospital
Chengdu, 610041, China
Southwest Hospital
Chongqing, 400038, China
First Affiliated Hospital of Dalian Medical University
Dalian, 116011, China
The Second Affiliated Hospital of Dalian Medical University
Dalian, 116027, China
Fujian Provincial Tumor Hospital
Fujian, 350014, China
Sun Yat-Sen University Cancer Center
Guangzhou, 510060, China
Guangdong General Hospital
Guangzhou, 510080, China
Sir Run Run Shaw Hospital
Hangzhou, 310016, China
Zhejiang Cancer Hospital
Hangzhou, 310022, China
The Third Affiliated Hospital of Harbin Medical University
Harbin, 150081, China
the 81th Hospital of PLA
Nanjing, 210002, China
Jiangsu Cancer Hospital
Nanjing, 210009, China
Shanghai Chest Hospital
Shanghai, 200030, China
Fudan University Shanghai Cancer Center
Shanghai, 200032, China
Shanghai Pulmonary Hospital
Shanghai, 200433, China
Tongji Hospital, Tongji University
Wuhan, 430030, China
Zhongshan Hospital Fudan University
Xuhui Area, Shanghai, 200032, China
Clinical Hospital Centar Sestre Milosrdnice
Zagreb, 10000, Croatia
UHC Zagreb
Zagreb, 10000, Croatia
University Hospital Brno
Brno, 625 00, Czechia
St. Anna Hospital, 2nd Internal Department
Brno, 656 53, Czechia
District Hospital Liberec
Liberec, 460 01, Czechia
Institut onkologie a rehabilitace Na Plesi s.r.o.
Nová Ves pod Pleší, 262 04, Czechia
District Hospital Pribram, Oncology Centrum
Příbram, 261 95, Czechia
Herlev Hospital
Herlev, 2730, Denmark
Odense Universitetshospital
Odense C, 5000, Denmark
HOP Croix Rousse, Pneumo, Lyon
Lyon, 69317, France
INS Paoli-Calmettes
Marseille, 13273, France
HOP Lyon Sud
Pierre-Bénite, 69495, France
CHU de Rouen - Hôpital de Bois Guillaume
Rouen, 76031, France
HOP Nord Laënnec
Saint-Herblain, 44805, France
Oncology Institute of the Loire
Saint-Priest-en-Jarez, 42271, France
HOP Civil
Strasbourg, 67091, France
Sainte Anne Training hospital for the armies
Toulon, 83401, France
Amtel Hospital first Clinical LLC
Tbilisi, 0079, Georgia
National Centre of Oncology
Tbilisi, 0177, Georgia
Chemotherapy & Immunotherapy Clinic 'Medulla', Tbilisi
Tbilisi, 0186, Georgia
Gemeinschaftspraxis Dr. Brudler / Dr. Heinrich, Augsburg
Augsburg, 86150, Germany
Zentralklinik Bad Berka GmbH
Bad Berka, 99437, Germany
Universitätsklinikum Benjamin Franklin, Berlin
Berlin, 12200, Germany
Helios Klinikum Emil von Behring
Berlin, 14165, Germany
Evangelische Lungenklinik Berlin
Buch, 13125, Germany
Gemeinschaftspraxis für Hämatologie und Onkologie, Köln
Cologne, 50677, Germany
Universitätsklinikum Frankfurt
Frankfurt, 60590, Germany
Krankenhaus Nordwest, Frankfurt
Frankfurt am Main, 60488, Germany
Klinikum Frankfurt Höchst GmbH
Frankfurt am Main, 65929, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Asklepios Fachkliniken München-Gauting
Gauting, 82131, Germany
Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH
Großhansdorf, 22927, Germany
Krankenhaus Martha-Maria Halle-Dölau gGmbH
Halle, 06120, Germany
Allgemeines Krankenhaus Harburg, 21075 Hamburg
Hamburg, 21075, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69126, Germany
Klinikum Kassel GmbH
Kassel, 34125, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Kiel, 24116, Germany
Universitätsklinikum Leipzig
Leipzig, 04103, Germany
POIS Leipzig GbR
Leipzig, 04357, Germany
Klinik, Löwenstein
Löwenstein, 74245, Germany
Universitätsklinikum Schleswig-Holstein, Campus Kiel
Lübeck, 23538, Germany
Katholisches Klinikum St. Hildegardiskrankenhaus, Mainz
Mainz, 55131, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, D-55131, Germany
Universitätsklinik links der Isar, München, Ziemssenstr. 1
München, 80336, Germany
Klinikum rechts der Isar der Technischen Universität München
München, 81675, Germany
Städt. Krankenhaus, München-Bogenhausen
München, 81925, Germany
Pius-Hospital, Oldenburg
Oldenburg, 26121, Germany
Universitätsklinikum Tübingen
Tübingen, 72076, Germany
Helios Dr. Horst Schmidt Kliniken Wiesbaden
Wiesbaden, 65199, Germany
Evangelisches Krankenhaus, Witten
Witten, 58455, Germany
Athens Hospital of Chest Diseasea "SOTIRIA"
Athens, 11527, Greece
University Hospital of Heraklion, University Pulmonology Cl
Heraklio, 71110, Greece
Iaso General Hospital
Holargos, Athens, 15562, Greece
Papageorgiou Hospital, 1st Cardiological Cl., Thessaloniki
Thessaloniki, 54603, Greece
General Hospital of Thessaloniki "G. Papanikolaou"
Thessaloniki, 57010, Greece
Vedanta Institute of Medical Sciences
Ahmedabad, 380009, India
KIDWAI memoraial Institute of oncology
Bangalore, 560029, India
Rajalakshmi Multispeciality Hospital
Bangalore, 560078, India
Jawaharlal Nehru Cancer Hospital & Research Centre
Bhopal, M.P., 462001, India
Apollo Hospital
Chennai, 600035, India
Birla Cancer Centre
Jaipur, 302004, India
Bhagwan Mahaveer Cancer Hospital & Research Center, Jawahar
Jaipur, 302017, India
SEAROC cancer center,S.K.soni Hospital
Jaipur, Rajasthan, 302013, India
B. P .Poddar Hospital & Medical Research Ltd.
Kolkata, West Bengal, 700053, India
Kasturba Medical College and Hospital
Mangalore, 575001, India
Tata Memorial Centre
Mumbai, 400012, India
Shatabdi Superspeciality Hospital
Nashik, 422005, India
Sir Gangaram Hospital
New Delhi, 110060, India
Indraprastha Apollo Hospitals
New Delhi, 110076, India
Rajiv Gandhi Cancer Institute and Research Centre
New Delhi, 110085, India
Jehangir Hospital Oncology Department
Pune, Maharahtra, 411001, India
Regional Cancer Center
Trivandrum, Kerala, 695011, India
City Cancer Centre, Cancer Hospital & Research
Vijayawada, 520002, India
King George Hospital
Visakhapatnam, 530002, India
E. Wolfson Medical Center, Holon 58100
Holon, 58100, Israel
Hadassah Medical Center, Ein-Karem
Jerusalem, 91120, Israel
Meir Medical Center
Kfar Saba, 44281, Israel
Sourasky Medical Center
Tel Aviv, 64239, Israel
The Chaim Sheba Medical Center Tel Hashomer
Tel Litwinsky, 52621, Israel
Assaf Harofe Medical Center
Ẕerifin, 70300, Israel
Az. Ospedaliere Umberto I di Ancona
Ancona, 60020, Italy
Centro di riferimento Oncologico
Aviano, 33081, Italy
Policlinico S. Orsola Malpighi
Bologna, 40135, Italy
Fond. Poliambulanza Istituto
Brescia, 25124, Italy
Azienda Ospedaliera Careggi
Florence, 50139, Italy
Ospedale Civile
Ivrea (TO), 10015, Italy
Istituto Scientifico Romagnolo
Meldola, 47014, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
Azienda Sanitaria Ospedale S. Luigi Gonzaga
Orbassano, 10043, Italy
Fondazione Salvatore Maugeri
Pavia, 27100, Italy
Ospedale S.Maria della Misericordia, AO di Perugia
Perugia, 06132, Italy
Hospital of Lithuanian Univ.of HealthSciences Kauno Klinikos
Kaunas, LT-50009, Lithuania
Siauliu ligonine, Siauliai
Šiauliai, 76307, Lithuania
Vilniaus Universiteto
Vilnius, LT-08661, Lithuania
Pulmonology Center in Bydgoszcz
Bydgoszcz, 85-326, Poland
Regional Complex Hospital
Elblag, 82-300, Poland
Institute of Tuberculosis & Pulmonology, III. Dept., Olsztyn
Olsztyn, 10-357, Poland
Mazowieckiego Centrum
Otwock, 05-400, Poland
Greater PL Cent.Pulmo.&Thor.Surg.Eugenia&Janusz Zeyland
Poznan, 60-569, Poland
Independent Public Hospital in Suwalki
Suwałki, 16-400, Poland
Specialist Hospital, Szczecin-Zdunowo
Szczecin, 70-891, Poland
Regional Specialist Hospital
Słupsk, 76-200, Poland
Onco.Cent. - Instit. of Maria Sklodowskiej-Curie
Warsaw, 02-781, Poland
IPO Porto Francisco Gentil, EPE
Coimbra, 3041-801, Portugal
IPO Lisboa Francisco Gentil, EPE
Lisbon, 1099-023, Portugal
CHLN, EPE - Hospital de Santa Maria
Lisbon, 1649-035, Portugal
IPO Porto Francisco Gentil, EPE
Porto, 4200-072, Portugal
Centro Hospitalar São João,EPE
Porto, 4200-319, Portugal
CHS, EPE - Hospital de São Bernardo
Setúbal, 2910, Portugal
Centro Hospitalar de Vila Nova de Gaia
Vila Nova de Gaia, 4434-502, Portugal
Baia Mare Emergency County Hospital
Baia Mare, 430031, Romania
Spitalul Clinic Judetean de Urgenta Brasov
Brasov, 500117, Romania
Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'
Bucharest, 022328, Romania
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
Cluj-Napoca, 400015, Romania
County Hospital "Dr. Alex Simionescu"
Hunedoara, 331057, Romania
Centrul de Oncologie Medicala
Iași, 700106, Romania
Emergency Clinical County Hospital "Sf Spiridon", Iasi
Iași, 700111, Romania
Onesti County Hospital
Onești, 601048, Romania
Emergency County Hospital "Sf.loan cel Nou"
Suceava, 720237, Romania
Oncomed SRL
Timișoara, 300239, Romania
SBIH of Arkhangelsk reg. "Arkhangelsk Clin. Onc. Dispensary"
Arkhangelsk, 163045, Russia
GLPU Cheliabinsky
Chelyabinsk, 454076, Russia
GUZ Irkutsk Regional Oncology Dispensary
Irkutsk, 664035, Russia
St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
Kazan', 420029, Russia
RBIH "Kursk regional clinical oncology dispensary"
Kursk, 305035, Russia
GUZ Regional Oncology Dispensary, Magnitogorsk
Magnitogorsk, 455001, Russia
FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF
Moscow, 115478, Russia
SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"
Pyatigorsk, 357502, Russia
GUZ "Regional Clinical Oncology Dispensary"
Ryazan, 390011, Russia
GUZ Leningradskaya Regional Clin. Hospital, St. Petersburg
Saint Petersburg, 194291, Russia
1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.
Saint Petersburg, 197022, Russia
SPb SBIH "City Clinical Oncological Dispensary"
Saint Petersburg, 197022, Russia
FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
Saint Petersburg, 197758, Russia
GUZ "Oncological Dispesary #2"
Sochi, 354057, Russia
GUZ Sverdlovsky Regional Oncology Dispensary
Yekaterinburg, 620036, Russia
Faculty Hospital Trnava
Trnava, 91775, Slovakia
GVI oncology Medi Clinic
Cape Town, 7570, South Africa
Parklands Hospital
Durban, 4091, South Africa
WCR CMJAH Clinical Trial Site
Johannesburg, 2193, South Africa
Medical Oncology Centre of Rosebank
Johannesburg, 2196, South Africa
Langenhoven Drive Oncology Centre
Port Elizabeth, 6045, South Africa
Pretoria Academic Hospital
Pretoria, 0001, South Africa
Wilgers oncology
Pretoria, 0041, South Africa
Gachon University Gil Medical Center
Incheon, 405760, South Korea
VHS Medical Center
Seoul, 05369, South Korea
The Catholic University of Korea, Seoul St.Mary's Hospital
Seoul, 137701, South Korea
Hospital Clínic de Barcelona
Barcelona, 08036, Spain
Hospital Universitario de Elche
Elche, 03202, Spain
Hospital Jerez de la Frontera
Jerez de La Frontera-Cádiz, 11407, Spain
Hospital La Princesa
Madrid, 28006, Spain
Hospital Quirónsalud Madrid
Pozuelo de Alarcón, 28233, Spain
Fundación Instituto Valenciano de Oncologia
Valencia, 46009, Spain
Servicio de Oncologia Radiotherapica
Valencia, 46010, Spain
Hospital Arnau de Vilanova
Valencia, 46015, Spain
Kantonsspital Aarau
Aarau, CH-5001, Switzerland
Kantonsspital Baden AG
Baden, CH-5404, Switzerland
Chernigiv Regional Oncology Centre
Chernihiv, 14029, Ukraine
Bukovynsk State Medical University
Chernivtsi, 58013, Ukraine
Chmelnytskyi Oblasnnyi Oncologichnyi Tsentr
Chmelnytskyi, 29000, Ukraine
City Clinical Hospital #4, Dnipropetrovsk State Medical Academy
Dnipropetrovsk, 49102, Ukraine
Donetsk Regional Antitumor Centre
Donetsk, 83000, Ukraine
Kharkiv Medical Acadamy of Postgraduate education
Kharkiv, 61070, Ukraine
Kryvorizskyi regional communal clinical oncology centre
Kryvyi Rig, 50048, Ukraine
Odesa Regional Oncological Centre
Odesa, 65055, Ukraine
Ternopil regional communal clinical oncology centre
Ternopil, 46023, Ukraine
Uzhgorod National University, Oncology Centre
Uzhhorod, 88000, Ukraine
Vinnytsia Regional Clinical Oncological Dispensary
Vinnytsia, 21029, Ukraine
Royal Bournemouth and Christchurch Hospital
Bournemouth, BH7 7DW, United Kingdom
Bristol Haematology & Onc. Ctr
Bristol, BS28ED, United Kingdom
Broomfield Hospital
Chelmsford, CM1 7ET, United Kingdom
Wythenshawe Hospital
Manchester, M23 9LT, United Kingdom
Poole Hospital
Poole, BH15 2JB, United Kingdom
Related Publications (2)
Gottfried M, Bennouna J, Bondarenko I, Douillard JY, Heigener DF, Krzakowski M, Mellemgaard A, Novello S, Orlov S, Summers Y, von Pawel J, Stohr J, Kaiser R, Reck M. Efficacy and Safety of Nintedanib Plus Docetaxel in Patients with Advanced Lung Adenocarcinoma: Complementary and Exploratory Analyses of the Phase III LUME-Lung 1 Study. Target Oncol. 2017 Aug;12(4):475-485. doi: 10.1007/s11523-017-0517-2.
PMID: 28702806DERIVEDReck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. doi: 10.1016/S1470-2045(13)70586-2. Epub 2014 Jan 9.
PMID: 24411639DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim Call Center
- Organization
- Boehringer Ingelheim Pharmaceuticals
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 8, 2008
First Posted
December 9, 2008
Study Start
December 3, 2008
Primary Completion
November 2, 2010
Study Completion
November 13, 2017
Last Updated
December 5, 2018
Results First Posted
December 1, 2014
Record last verified: 2018-11