Nintedanib (BIBF 1120) in Mesothelioma

Mesothelioma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01907100
• Other study ID #: 1199.93
• Secondary ID: 2012-005201-48
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: September 19, 2013
• Est. completion date: August 31, 2018

Study information

• Verified date: March 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 545
• Est. completion date: August 31, 2018
• Est. primary completion date: March 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mesothelioma

Intervention

Drug:
• Nintedanib
triple kinase inhibitor; 200mg starting dose
• Pemetrexed
backbone chemo
• Cisplatin
backbone chemo
• Cisplatin
backbone chemo
• Pemetrexed
backbone chemo
• Placebo
Nintedanib matching placebo

Locations

Country	Name	City	State
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autónoma de Bs As
Argentina	Sanatorio Güemes	Ciudad Autónoma de Bs As
Argentina	Clínica Universitaria Reina Fabiola	Ciudad de Cordoba
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Peninsula Haematology & Oncology	Frankston	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Perth Oncology	Perth	Western Australia
Australia	Mater Cancer Care Centre	South Brisbane	Queensland
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	Calvary Mater Newcastle Hospital	Waratah	New South Wales
Australia	Border Onclogy Research	Wodonga	Victoria
Austria	LKH Leoben	Leoben
Austria	AKH - Medical University of Vienna	Vienna
Austria	Klinikum Wels - Grieskirchen GmbH	Wels
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
Belgium	Edegem - UNIV UZ Antwerpen	Edegem
Belgium	UNIV UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	AZ Sint-Maarten	Mechelen
Canada	QEII Health Sciences Centre (Dalhousie University)	Halifax	Nova Scotia
Canada	IUCPQ (Laval University)	Quebec
Canada	Health Sciences North	Sudbury	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Chile	Centro Internacional de Estudios Clínicos - CIEC	Recoleta
Chile	Orlandi Oncologia	Vitacura
Croatia	University Clinic for Pulmonary Diseases	Zagreb
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Olomouc	Olomouc
Denmark	Rigshospitalet, København, Onkologisk afdeling	Købenahvn Ø
Egypt	Clinical Research Center Alexandria	Alexandria
Egypt	Medical Research Institute	Alexandria
Egypt	Nasser Institute	Cairo
Egypt	National Cancer Institute, Cairo University	Cairo
France	CLI Bordeaux Nord Aquitaine	Bordeaux
France	HOP Morvan	Brest
France	HOP Côte de Nacre	Caen
France	HOP Calmette	Lille
France	HOP Nord	Marseille
France	HOP Lyon Sud	Pierre-Bénite
France	HOP HIA Saint-Anne	Toulon
France	HOP Larrey	Toulouse
France	INS Gustave Roussy	Villejuif
Germany	Helios Klinikum Emil von Behring	Berlin
Germany	Vivantes Netzwerk für Gesundheit GmbH	Berlin
Germany	Klinik Schillerhöhe GmbH	Gerlingen
Germany	Pneumologisches Forschungsinstitut an der LungenClinic Grosshansdorf GmbH	Großhansdorf
Germany	Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum des Saarlandes	Homburg/Saar
Germany	Klinik, Löwenstein	Löwenstein
Israel	Rambam Medical Center	Haifa
Israel	Rabin Medical Center Beilinson	Petach Tikva
Israel	Sourasky Medical Center	Tel-Aviv
Italy	Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Centro di riferimento Oncologico	Aviano (PN)
Italy	Humanitas Gavazzeni	Bergamo
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genova
Italy	Azienda Sanitaria Ospedale S. Luigi Gonzaga	Orbassano (TO)
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Japan	University Hospital of Occupational and Environmental Health	Fukuoka, Kitakyushu
Japan	Hyogo Prefectural Amagasaki General Medical Center	Hyogo, Amagasaki
Japan	Hyogo College of Medicine Hospital	Hyogo, Nishinomiya
Japan	Yokosuka Kyosai Hospital	Kanagawa , Yokosuka
Japan	Japan Labour Health and Safety Organization Okayama Rosai Hospital	Okayama, Okayama
Japan	Otemae Hospital	Osaka, Osaka
Japan	Kindai University Hospital	Osaka, OsakaSayama
Japan	Juntendo University Hospital	Tokyo, Bunkyo-ku
Mexico	Centro Oncologico de Chihuahua	Chihuahua
Mexico	Instituto Nacional de Cancerologia	Mexico
Mexico	Centro Oncologico Estatal ISSEMYM	Toluca
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Erasmus Medisch Centrum	Rotterdam
Norway	Oslo Universitetssykehus HF, Radiumhospitalet	Oslo
Norway	St. Olavs Hospital, Universitetssykehuset i Trondheim	Trondheim
Poland	University Clinical Center, Gdansk	Gdansk
Poland	Clin.Hosp.Med.Univ.Marcinkowski in Poznan	Poznan
Poland	Greater PL Cent.Pulmo.&Thor.Surg.Eugenia&Janusz Zeyland	Poznan
Poland	Onco.Cent. - Instit. of Maria Sklodowskiej-Curie	Warsaw
Portugal	Centro Hospitalar Lisboa Norte Hospital Pulido Valente	Lisboa
Portugal	Hospital CUF Porto	Porto
Russian Federation	St.Budg.Heal.Inst."Chelyabinsk Reg.Clin.Cen.Onc&Nucl.Med"	Chelyabinsk
Russian Federation	St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"	Kazan
Russian Federation	FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF	Moscow
Russian Federation	1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.	Saint-Petersburg
Russian Federation	FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF	Saint-Petersburg
Russian Federation	SBI HC-Rep.Clin.Onc.Disp.MoH.Rep.Bashkortostan	Ufa
South Africa	Wilgers Oncology Centre	Pretoria
Spain	Hospital Universitario de Cruces	Barakaldo (Vizcaya)
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Donostia	Donostia (Gipuzkoa)
Spain	Hospital Duran i Reynals	L'Hospitalet de Llobregat
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Virgen del Rocío	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Sweden	Sahlgrenska US, Göteborg	Göteborg
Sweden	Universitetssjukhuset, Linköping	Linköping
Sweden	Skånes universitetssjukhus, Lund	Lund
Sweden	Karolinska Univ. sjukhuset	Stockholm
Sweden	Akademiska sjukhuset	Uppsala
Turkey	Eskisehir Osmangazi Üni. Sag. Uygulama ve Arastirma Has.	Eskisehir
Turkey	Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Dr.Suat Seren EAH	Izmir
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Guy's Hospital	London
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	The Royal Marsden Hospital	Sutton
United Kingdom	Wythenshawe Hospital	Wythenshawe
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Greenville Health System	Greenville	South Carolina
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	Texas Oncology - McAllen	McAllen	Texas
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Texas Oncology-San Antonio Northeast	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Cancer Care Northwest Centers, PS	Spokane Valley	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  Croatia,  Czechia,  Denmark,  Egypt,  France,  Germany,  Israel,  Italy,  Japan,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Russian Federation,  South Africa,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	Overall survival was defined as the duration of time from randomization to time of death.; This is the key secondary endpoint of the trial.	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	Objective Response According to Modified RECIST- Investigator Assessment	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.	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
Secondary	Disease Control According to Modified RECIST- Investigator Assessment	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.	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

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