Nintedanib (BIBF 1120) in Mesothelioma

NCT01907100 | Terminated Phase 2 Results

• 2 other identifiers: 1199.932012-005201-48
• Study Type: interventional
• Target: 545
• Locations: 26 countries
• Sites: 113

Brief Summary

This is a phase II/III confirmatory study designed to evaluate the safety and efficacy of nintedanib (BIBF 1120) in combination + (pemetrexed / cisplatin) followed by nintedanib (BIBF 1120) versus placebo + pemetrexed / cisplatin followed by placebo for the treatment of patients with unresectable malignant pleural mesothelioma.

Conditions

Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  This outcome measure presents progression-free survival. Disease progression was defined according to the modified Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Progression-free survival time was calculated as the duration from the date of randomization to the date of disease progression or death, whichever occurred first. For patients with known date of progression (or death): PFS (days) = min (date of progression, date of death) - date of randomization + 1 day. For patients without progression or death, PFS was censored at the last imaging date that showed no disease progression: PFS (days, censored) = date of last imaging showing no progression - date randomization + 1 day.

  From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months)

Secondary Outcomes (3)

• Overall Survival (OS)

  From randomization until the earliest of disease progression, death or (Phase II: cut-off date of 4-March-2016; up to 889 days) (Phase III: cut-off date of 16-March-2018; up to 31 months)

• Objective Response According to Modified RECIST- Investigator Assessment

  Tumour imaging was to be performed every 6 weeks until disease progression, death or start of subsequent anti-cancer therapy, whichever occurred earlier; up to 54 months

• Disease Control According to Modified RECIST- Investigator Assessment

  Tumour imaging was to be performed every 6 weeks until disease progression, death or start of subsequent anti-cancer therapy, whichever occurred earlier; up to 54 months

Study Arms (2)

Placebo + pemetrexed/cisplatin

PLACEBO COMPARATOR

Placebo controlled arm

Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo

Nintedanib 200mg + pemetrexed/cisplatin

EXPERIMENTAL

Experimental arm

Drug: Nintedanib; Drug: Cisplatin; Drug: Pemetrexed

Interventions

Nintedanib DRUG

triple kinase inhibitor; 200mg starting dose

Nintedanib 200mg + pemetrexed/cisplatin

Pemetrexed DRUG

backbone chemo

Placebo + pemetrexed/cisplatin

Cisplatin DRUG

backbone chemo

Nintedanib 200mg + pemetrexed/cisplatin

Placebo DRUG

Nintedanib matching placebo

Placebo + pemetrexed/cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed malignant pleural mesothelioma (MPM) (Epithelioid or biphasic subtype for Phase II patients; epithelioid subtype only for Phase III patients)
• Life expectancy of at least 3 months in the opinion of the investigator
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Measurable disease according to modified RECIST (Response Evaluation Criteria In Solid Tumours) criteria

You may not qualify if:

• Previous systemic chemotherapy for MPM
• Prior treatment with nintedanib or any other prior line of therapy
• Phase II patients with sarcomatoid subtype MPM or Phase III patients with biphasic or sarcomatoid subtype MPM
• Patients with symptomatic neuropathy
• Radiotherapy (except extremities) within 3 months prior to baseline imaging
• Active brain metastases (e.g. stable for \< 4 weeks)
• Radiographic evidence of cavitary or necrotic tumours or local invasion of major blood vessels by MPM
• Significant cardiovascular diseases
• Inadequate hematologic, renal, or hepatic function

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (123)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Rocky Mountain Cancer Centers

Littleton, Colorado, 80120-4413, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89052, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Greenville Health System

Greenville, South Carolina, 29615, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology - McAllen

McAllen, Texas, 78503, United States

Location

Texas Oncology-San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Cancer Care Northwest Centers, PS

Spokane Valley, Washington, 99216, United States

Location

Sanatorio Güemes

Ciudad Autónoma de Bs As, C1180AAX, Argentina

Location

Instituto Medico Especializado Alexander Fleming

Ciudad Autónoma de Bs As, C1426ANZ, Argentina

Location

Clínica Universitaria Reina Fabiola

Córdoba, X5004FHP, Argentina

Location

Northern Cancer Institute

St Leonards, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle Hospital

Waratah, New South Wales, 2298, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Mater Cancer Care Centre

South Brisbane, Queensland, 4101, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Peninsula Haematology & Oncology

Frankston, Victoria, 3199, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Border Onclogy Research

Wodonga, Victoria, 3690, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Perth Oncology

Perth, Western Australia, 6000, Australia

Location

LKH Leoben

Leoben, 8700, Austria

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

Klinikum Wels - Grieskirchen GmbH

Wels, 4600, Austria

Location

Brussels - UNIV Saint-Luc

Brussels, 1200, Belgium

Location

Edegem - UNIV UZ Antwerpen

Edegem, 2650, Belgium

Location

UNIV UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

AZ Sint-Maarten

Mechelen, 2800, Belgium

Location

QEII Health Sciences Centre (Dalhousie University)

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

IUCPQ (Laval University)

Québec, GLV 4G5, Canada

Location

Centro Internacional de Estudios Clínicos - CIEC

Recoleta, 8420383, Chile

Location

Orlandi Oncologia

Vitacura, 7630372, Chile

Location

University Clinic for Pulmonary Diseases

Zagreb, 10000, Croatia

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

University Hospital Olomouc

Olomouc, 779 00, Czechia

Location

Rigshospitalet, København, Onkologisk afdeling

Købenahvn Ø, 2100, Denmark

Location

Clinical Research Center Alexandria

Alexandria, 21131, Egypt

Location

Medical Research Institute

Alexandria, 21648, Egypt

Location

National Cancer Institute, Cairo University

Cairo, 11796, Egypt

Location

Nasser Institute

Cairo, 12655, Egypt

Location

CLI Bordeaux Nord Aquitaine

Bordeaux, 33000, France

Location

HOP Morvan

Brest, 29609, France

Location

HOP Côte de Nacre

Caen, 14033, France

Location

HOP Calmette

Lille, 59000, France

Location

HOP Nord

Marseille, 13015, France

Location

HOP Lyon Sud

Pierre-Bénite, 69230, France

Location

HOP HIA Saint-Anne

Toulon, 83800, France

Location

HOP Larrey

Toulouse, 31059, France

Location

INS Gustave Roussy

Villejuif, 94805, France

Location

Vivantes Netzwerk für Gesundheit GmbH

Berlin, 12351, Germany

Location

Helios Klinikum Emil von Behring

Berlin, 14165, Germany

Location

Klinik Schillerhöhe GmbH

Gerlingen, 70839, Germany

Location

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

Location

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Universitätsklinikum des Saarlandes

Homburg/Saar, 66421, Germany

Location

Klinik, Löwenstein

Löwenstein, 74245, Germany

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Rabin Medical Center Beilinson

Petah Tikva, 49100, Israel

Location

Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo

Alessandria, 15121, Italy

Location

Centro di riferimento Oncologico

Aviano (PN), 33081, Italy

Location

Humanitas Gavazzeni

Bergamo, 24125, Italy

Location

Istituto Nazionale per la Ricerca sul Cancro

Genova, 16132, Italy

Location

Azienda Sanitaria Ospedale S. Luigi Gonzaga

Orbassano (TO), 10043, Italy

Location

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

Location

University Hospital of Occupational and Environmental Health

Fukuoka, Kitakyushu, 807-8556, Japan

Location

Hyogo Prefectural Amagasaki General Medical Center

Hyogo, Amagasaki, 660-8550, Japan

Location

Hyogo College of Medicine Hospital

Hyogo, Nishinomiya, 663-8501, Japan

Location

Yokosuka Kyosai Hospital

Kanagawa , Yokosuka, 238-8558, Japan

Location

Japan Labour Health and Safety Organization Okayama Rosai Hospital

Okayama, Okayama, 702-8055, Japan

Location

Kindai University Hospital

Osaka, OsakaSayama, 589-8511, Japan

Location

Otemae Hospital

Osaka, Osaka, 540-0008, Japan

Location

Juntendo University Hospital

Tokyo, Bunkyo-ku, 113-8431, Japan

Location

Centro Oncologico de Chihuahua

Chihuahua City, 31217, Mexico

Location

Instituto Nacional de Cancerologia

México, 14080, Mexico

Location

Centro Oncologico Estatal ISSEMYM

Toluca, 50180, Mexico

Location

Medisch Spectrum Twente

Enschede, 7513 ER, Netherlands

Location

Zuyderland Medisch Centrum

Heerlen, 6419 PC, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 CE, Netherlands

Location

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, N-0310, Norway

Location

St. Olavs Hospital, Universitetssykehuset i Trondheim

Trondheim, N-7006, Norway

Location

University Clinical Center, Gdansk

Gdansk, 80-952, Poland

Location

Clin.Hosp.Med.Univ.Marcinkowski in Poznan

Poznan, 60-569, Poland

Location

Greater PL Cent.Pulmo.&Thor.Surg.Eugenia&Janusz Zeyland

Poznan, 60-569, Poland

Location

Onco.Cent. - Instit. of Maria Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Centro Hospitalar Lisboa Norte Hospital Pulido Valente

Lisbon, 1769-001, Portugal

Location

Hospital CUF Porto

Porto, 4100-180, Portugal

Location

St.Budg.Heal.Inst."Chelyabinsk Reg.Clin.Cen.Onc&Nucl.Med"

Chelyabinsk, 454087, Russia

Location

St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"

Kazan', 420029, Russia

Location

FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF

Moscow, 115478, Russia

Location

1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.

Saint Petersburg, 197022, Russia

Location

FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF

Saint Petersburg, 197758, Russia

Location

SBI HC-Rep.Clin.Onc.Disp.MoH.Rep.Bashkortostan

Ufa, 450054, Russia

Location

Wilgers Oncology Centre

Pretoria, 0041, South Africa

Location

Hospital Universitario de Cruces

Barakaldo (Vizcaya), 48903, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Donostia

Donostia (Gipuzkoa), 20080, Spain

Location

Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Sahlgrenska US, Göteborg

Gothenburg, 413 45, Sweden

Location

Universitetssjukhuset, Linköping

Linköping, 581 85, Sweden

Location

Skånes universitetssjukhus, Lund

Lund, 221 85, Sweden

Location

Karolinska Univ. sjukhuset

Stockholm, 171 76, Sweden

Location

Akademiska sjukhuset

Uppsala, 751 85, Sweden

Location

Eskisehir Osmangazi Üni. Sag. Uygulama ve Arastirma Has.

Eskişehir, 26950, Turkey (Türkiye)

Location

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi

Istanbul, 34899, Turkey (Türkiye)

Location

Dr.Suat Seren EAH

Izmir, 35120, Turkey (Türkiye)

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Wythenshawe Hospital

Wythenshawe, M23 9LT, United Kingdom

Location

Related Publications (1)

• Scagliotti GV, Gaafar R, Nowak AK, Nakano T, van Meerbeeck J, Popat S, Vogelzang NJ, Grosso F, Aboelhassan R, Jakopovic M, Ceresoli GL, Taylor P, Orlandi F, Fennell DA, Novello S, Scherpereel A, Kuribayashi K, Cedres S, Sorensen JB, Pavlakis N, Reck M, Velema D, von Wangenheim U, Kim M, Barrueco J, Tsao AS. Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2019 Jul;7(7):569-580. doi: 10.1016/S2213-2600(19)30139-0. Epub 2019 May 15.

  PMID: 31103412 DERIVED

MeSH Terms

Conditions

Mesothelioma

Interventions

nintedanib; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

In accordance with the specifications in the protocol, the trial was discontinued prematurely after the primary PFS analysis not because of any safety concerns but rather due to failure to meet the efficacy target.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2013
• First Posted: July 24, 2013
• Study Start: September 19, 2013
• Primary Completion: March 16, 2018
• Study Completion: August 31, 2018
• Last Updated: March 18, 2019
• Results First Posted: March 18, 2019

Record last verified: 2019-03

Locations

NL (3); BE (5); CZ (2); DE (7); FR (9); PT (2); RU (6); EG (4); AU (3); US (10); ZA (1); CA (4); DK (1); IT (6); ES (9); SE (5); PL (4); TU (3); NO (2); CL (2); ME (3); AR (3); GB (7); CR (1); IL (3); JP (8)