Nintedanib (BIBF 1120) in Mesothelioma

• ClinicalTrials.gov Identifier: NCT01907100
• Recruitment Status: Terminated
• First Posted: July 24, 2013
• Results First Posted: March 18, 2019
• Last Update Posted: March 18, 2019
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Drug: Nintedanib; Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 545 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: LUME-Meso: Double Blind, Randomised, Multicentre, Phase II/III Study of Nintedanib in Combination With Pemetrexed / Cisplatin Followed by Continuing Nintedanib Monotherapy Versus Placebo in Combination With Pemetrexed / Cisplatin Followed by Continuing Placebo Monotherapy for the Treatment of Patients With Unresectable Malignant Pleural Mesothelioma
• Actual Study Start Date: September 19, 2013
• Actual Primary Completion Date: March 16, 2018
• Actual Study Completion Date: August 31, 2018

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo + pemetrexed/cisplatin; Placebo controlled arm	Drug: Pemetrexed; backbone chemo; Drug: Cisplatin; backbone chemo; Drug: Placebo; Nintedanib matching placebo
Experimental: Nintedanib 200mg + pemetrexed/cisplatin; Experimental arm	Drug: Nintedanib; triple kinase inhibitor; 200mg starting dose; Drug: Cisplatin; backbone chemo; Drug: Pemetrexed; backbone chemo

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: 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) ]
   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.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 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) ]

   Overall survival was defined as the duration of time from randomization to time of death.

   This is the key secondary endpoint of the trial.

2. Objective Response According to Modified RECIST- Investigator Assessment [ Time Frame: 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 ]

   Objective response (best overall tumour response of confirmed complete response [CR] or confirmed partial response [PR]).

   Complete Response: disappearance of all target lesions Partial Response: at least a 30 % decrease in the total tumour measurement of target lesions, taking as reference the baseline total tumour measurement.

   Percentage of Patients with confirmed objective response is presented. This endpoint was only evaluated for Phase III part.

3. Disease Control According to Modified RECIST- Investigator Assessment [ Time Frame: 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 (best overall response of confirmed CR or PR, or Stable Disease (SD) that lasted ≥36 days) according to modified RECIST.

   Percentage of Patients with Disease control is presented. This endpoint was only evaluated for Phase III part.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

• 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

Exclusion criteria:

• 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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35249

United States, California

University of California San Francisco

San Francisco, California, United States, 94115

United States, Colorado

Rocky Mountain Cancer Centers

Littleton, Colorado, United States, 80120-4413

United States, Nevada

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States, 89052

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15232

United States, South Carolina

Greenville Health System

Greenville, South Carolina, United States, 29615

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Texas Oncology - McAllen

McAllen, Texas, United States, 78503

Texas Oncology-San Antonio Northeast

San Antonio, Texas, United States, 78217

United States, Washington

Cancer Care Northwest Centers, PS

Spokane Valley, Washington, United States, 99216

Argentina

Sanatorio Güemes

Ciudad Autónoma de Bs As, Argentina, C1180AAX

Instituto Medico Especializado Alexander Fleming

Ciudad Autónoma de Bs As, Argentina, C1426ANZ

Clínica Universitaria Reina Fabiola

Ciudad de Cordoba, Argentina, X5004FHP

Australia, New South Wales

Northern Cancer Institute

St Leonards, New South Wales, Australia, 2065

Calvary Mater Newcastle Hospital

Waratah, New South Wales, Australia, 2298

Australia, Queensland

The Prince Charles Hospital

Chermside, Queensland, Australia, 4032

Mater Cancer Care Centre

South Brisbane, Queensland, Australia, 4101

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Peninsula Haematology & Oncology

Frankston, Victoria, Australia, 3199

Austin Health

Heidelberg, Victoria, Australia, 3084

Border Onclogy Research

Wodonga, Victoria, Australia, 3690

Australia, Western Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia, 6009

Perth Oncology

Perth, Western Australia, Australia, 6000

Austria

LKH Leoben

Leoben, Austria, 8700

AKH - Medical University of Vienna

Vienna, Austria, 1090

Klinikum Wels - Grieskirchen GmbH

Wels, Austria, 4600

Belgium

Brussels - UNIV Saint-Luc

Bruxelles, Belgium, 1200

Edegem - UNIV UZ Antwerpen

Edegem, Belgium, 2650

UNIV UZ Gent

Gent, Belgium, 9000

UZ Leuven

Leuven, Belgium, 3000

AZ Sint-Maarten

Mechelen, Belgium, 2800

Canada, Nova Scotia

QEII Health Sciences Centre (Dalhousie University)

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

Health Sciences North

Sudbury, Ontario, Canada, P3E 5J1

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada

IUCPQ (Laval University)

Quebec, Canada, GLV 4G5

Chile

Centro Internacional de Estudios Clínicos - CIEC

Recoleta, Chile, 8420383

Orlandi Oncologia

Vitacura, Chile, 7630372

Croatia

University Clinic for Pulmonary Diseases

Zagreb, Croatia, 10000

Czechia

University Hospital Brno

Brno, Czechia, 625 00

University Hospital Olomouc

Olomouc, Czechia, 779 00

Denmark

Rigshospitalet, København, Onkologisk afdeling

Købenahvn Ø, Denmark, 2100

Egypt

Clinical Research Center Alexandria

Alexandria, Egypt, 21131

Medical Research Institute

Alexandria, Egypt, 21648

National Cancer Institute, Cairo University

Cairo, Egypt, 11796

Nasser Institute

Cairo, Egypt, 12655

France

CLI Bordeaux Nord Aquitaine

Bordeaux, France, 33000

HOP Morvan

Brest, France, 29609

HOP Côte de Nacre

Caen, France, 14033

HOP Calmette

Lille, France, 59000

HOP Nord

Marseille, France, 13015

HOP Lyon Sud

Pierre-Bénite, France, 69230

HOP HIA Saint-Anne

Toulon, France, 83800

HOP Larrey

Toulouse, France, 31059

INS Gustave Roussy

Villejuif, France, 94805

Germany

Vivantes Netzwerk für Gesundheit GmbH

Berlin, Germany, 12351

Helios Klinikum Emil von Behring

Berlin, Germany, 14165

Klinik Schillerhöhe GmbH

Gerlingen, Germany, 70839

Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH

Großhansdorf, Germany, 22927

Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg

Heidelberg, Germany, 69126

Universitätsklinikum des Saarlandes

Homburg/Saar, Germany, 66421

Klinik, Löwenstein

Löwenstein, Germany, 74245

Israel

Rambam Medical Center

Haifa, Israel, 31096

Rabin Medical Center Beilinson

Petach Tikva, Israel, 49100

Sourasky Medical Center

Tel-Aviv, Israel, 64239

Italy

Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo

Alessandria, Italy, 15121

Centro di riferimento Oncologico

Aviano (PN), Italy, 33081

Humanitas Gavazzeni

Bergamo, Italy, 24125

Istituto Nazionale per la Ricerca sul Cancro

Genova, Italy, 16132

Azienda Sanitaria Ospedale S. Luigi Gonzaga

Orbassano (TO), Italy, 10043

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

Siena, Italy, 53100

Japan

University Hospital of Occupational and Environmental Health

Fukuoka, Kitakyushu, Japan, 807-8556

Hyogo Prefectural Amagasaki General Medical Center

Hyogo, Amagasaki, Japan, 660-8550

Hyogo College of Medicine Hospital

Hyogo, Nishinomiya, Japan, 663-8501

Yokosuka Kyosai Hospital

Kanagawa , Yokosuka, Japan, 238-8558

Japan Labour Health and Safety Organization Okayama Rosai Hospital

Okayama, Okayama, Japan, 702-8055

Kindai University Hospital

Osaka, OsakaSayama, Japan, 589-8511

Otemae Hospital

Osaka, Osaka, Japan, 540-0008

Juntendo University Hospital

Tokyo, Bunkyo-ku, Japan, 113-8431

Mexico

Centro Oncologico de Chihuahua

Chihuahua, Mexico, 31217

Instituto Nacional de Cancerologia

Mexico, Mexico, 14080

Centro Oncologico Estatal ISSEMYM

Toluca, Mexico, 50180

Netherlands

Medisch Spectrum Twente

Enschede, Netherlands, 7513 ER

Zuyderland Medisch Centrum

Heerlen, Netherlands, 6419 PC

Erasmus Medisch Centrum

Rotterdam, Netherlands, 3015 CE

Norway

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, Norway, N-0310

St. Olavs Hospital, Universitetssykehuset i Trondheim

Trondheim, Norway, N-7006

Poland

University Clinical Center, Gdansk

Gdansk, Poland, 80-952

Clin.Hosp.Med.Univ.Marcinkowski in Poznan

Poznan, Poland, 60-569

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

Poznan, Poland, 60-569

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

Warsaw, Poland, 02-781

Portugal

Centro Hospitalar Lisboa Norte Hospital Pulido Valente

Lisboa, Portugal, 1769-001

Hospital CUF Porto

Porto, Portugal, 4100-180

Russian Federation

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

Chelyabinsk, Russian Federation, 454087

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

Kazan, Russian Federation, 420029

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

Moscow, Russian Federation, 115478

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

Saint-Petersburg, Russian Federation, 197022

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

Saint-Petersburg, Russian Federation, 197758

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

Ufa, Russian Federation, 450054

South Africa

Wilgers Oncology Centre

Pretoria, South Africa, 0041

Spain

Hospital Universitario de Cruces

Barakaldo (Vizcaya), Spain, 48903

Hospital Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clínic de Barcelona

Barcelona, Spain, 08036

Hospital Universitario Donostia

Donostia (Gipuzkoa), Spain, 20080

Hospital Duran i Reynals

L'Hospitalet de Llobregat, Spain, 08907

Hospital Ramón y Cajal

Madrid, Spain, 28034

Hospital Virgen de la Victoria

Malaga, Spain, 29010

Hospital Virgen del Rocío

Sevilla, Spain, 41013

Hospital Clínico de Valencia

Valencia, Spain, 46010

Sweden

Sahlgrenska US, Göteborg

Göteborg, Sweden, 413 45

Universitetssjukhuset, Linköping

Linköping, Sweden, 581 85

Skånes universitetssjukhus, Lund

Lund, Sweden, 221 85

Karolinska Univ. sjukhuset

Stockholm, Sweden, 171 76

Akademiska sjukhuset

Uppsala, Sweden, 751 85

Turkey

Eskisehir Osmangazi Üni. Sag. Uygulama ve Arastirma Has.

Eskisehir, Turkey, 26950

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi

Istanbul, Turkey, 34899

Dr.Suat Seren EAH

Izmir, Turkey, 35120

United Kingdom

Western General Hospital

Edinburgh, United Kingdom, EH4 2XU

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

Leicester Royal Infirmary

Leicester, United Kingdom, LE1 5WW

Guy's Hospital

London, United Kingdom, SE1 9RT

The Royal Marsden Hospital

London, United Kingdom, SW3 6JJ

The Royal Marsden Hospital

Sutton, United Kingdom, SM2 5PT

Wythenshawe Hospital

Wythenshawe, United Kingdom, M23 9LT

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:

Study Protocol  [PDF] June 22, 2016

Statistical Analysis Plan  [PDF] December 8, 2016

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Sørensen 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.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01907100
• Other Study ID Numbers: 1199.93; 2012-005201-48 ( EudraCT Number )
• First Posted: July 24, 2013
• Results First Posted: March 18, 2019
• Last Update Posted: March 18, 2019
• Last Verified: March 2019

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Cisplatin; Pemetrexed; Nintedanib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors