Clinical trial NCT01456325: A Study of Onartuzumab (MetMAb) in Combination With Tarceva (Erlotinib) in Participants With Met Diagnostic-Positive Non-Small Cell Lung Cancer Who Have Received Chemotherapy For Advanced or Metastatic Disease (MetLung)
Official title: A Randomized, Phase III, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating Efficacy and Safety of Onartuzumab (Metmab) in Combination With Tarceva (Erlotinib) in Patients With Met Diagnostic-Positive Non-Small Cell Lung Cancer Who Have Received Standard Chemotherapy for Advanced/Metastatic Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2011-10-20
Enrollment: 494
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, multicenter, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with Tarceva (erlotinib) in participants with incurable non-small cell lung cancer identified to be Met diagnostic-positive. Participants will be randomized to receive either onartuzumab (MetMAb) or placebo in combination with erlotinib. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.


Eligibility criteria: Inclusion Criteria:

* Adult participants, greater than or equal to (\>/=) 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Histologically or cytologically confirmed incurable Stage IIIb/IV NSCLC tumor
* Met diagnostic-positive status tested by immunohistochemistry (IHC)
* Results of endothelial growth factor receptor (EGFR)-activating mutation testing
* Radiographic evidence of disease
* Prior treatment with at least one platinum-based line of treatment (for stage IIIb/IV) and no more than one additional line of chemotherapy treatment; the last dose of chemotherapy must have been administered \>/= 21 days prior to Day 1
* availability of tissue sample for diagnostic testing is required

Exclusion Criteria:

* More than 30 days of exposure to an investigational or marketed agent that can act by EGFR inhibition, or a known EGFR-related toxicity resulting in dose modifications (EGFR inhibitors including but not limited to gefitinib, erlotinib and cetuximab)
* Brain metastases or spinal cord compression not definitively treated with surgery and/or radiation, or previously treated central nervous system (CNS) metastases or spinal cord compression without evidence of stable disease for \>/= 14 days
* History of another malignancy in the previous 3 years, unless cured by surgery alone and continuously disease free for at least 3 years; participants with prior history of non-invasive cancers are eligible
* Inadequate hematological, biochemical or organ function
* Significant history of cardiac disease
* Serious active infection at time of randomization or other serious underlying medical conditions that would impair the ability of the participant to receive protocol treatment
* Any inflammatory changes of the surface of the eye
* Clinically significant gastro-intestinal disease, including uncontrolled inflammatory gastro-intestinal diseases
* Pregnant or lactating women
* Positive for human immunodefinciency (HIV) infection

Primary outcomes:
measure: Overall Survival
timeFrame: Randomization until death (up to approximately 18 months) (assessed at the treating physician's discretion using the local standard-of-care practice)
Secondary outcomes:
measure: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) Scores
timeFrame: Screening, Day 1 of Cycles 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 (cycle length = 21 days), study drug discontinuation visit (up to approximately 18 months)
measure: Onartuzumab Serum Concentrations
timeFrame: 1 hour pre-onartuzumab (Pr-O) infusion on Day 1 of Cycles 1, 2, and 4, 1 hour post-onartuzumab (Po-O) infusion on Day 1 of Cycle 1 (cycle length = 21 days and duration of infusion = 60 minutes), End of treatment (up to approximately 18 months)
measure: Percentage of Participants With Disease Progression or Death
timeFrame: Randomization until disease progression or death, whichever occurred first (up to approximately 18 months) (assessed at the treating physician's discretion using the local standard-of-care practice)
measure: Progression Free Survival (PFS)
timeFrame: Randomization until disease progression or death, whichever occurred first (up to approximately 18 months) (assessed at the treating physician's discretion using the local standard-of-care practice)
measure: Percentage of Participants with an Objective Response Assessed Using RECIST V 1.1
timeFrame: Randomization until disease progression or death, whichever occurred first (up to approximately 18 months) (assessed at the treating physician's discretion using the local standard-of-care practice)
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Hayward
country: United States
state: California
city: Modesto
country: United States
state: California
city: Oakland
country: United States
state: California
city: Orange
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Jose
country: United States
state: California
city: Santa Clara
country: United States
state: California
city: South San Francisco
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Boca Raton
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Urbana
country: United States
state: Illinois
city: Bettendorf
country: United States
state: Iowa
city: Sioux City
country: United States
state: Iowa
city: Louisville
country: United States
state: Kentucky
city: Annapolis
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Duluth
country: United States
state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Reno
country: United States
state: Nevada
city: Farmington
country: United States
state: New Mexico
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Cleveland
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state: Ohio
city: Columbus
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state: Ohio
city: Columbus
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state: Ohio
city: Philadelphia
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state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Columbia
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state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
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state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Bristol
country: United States
state: Virginia
city: Roanoke
country: United States
state: Virginia
city: La Plata
country: Argentina
city: Quilmes
country: Argentina
city: Santa Fe
country: Argentina
city: Camperdown
country: Australia
state: New South Wales
city: Waratah
country: Australia
state: New South Wales
city: Chermside
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Parkville
country: Australia
state: Victoria
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Gilly (Charleroi)
country: Belgium
city: Liège
country: Belgium
city: Namur
country: Belgium
city: Salvador/BA
country: Brazil
state: BA
city: Lajeado
country: Brazil
state: RS
city: Novo Hamburgo
country: Brazil
state: RS
city: Jau
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sorocaba
country: Brazil
state: SP
city: Saint John
country: Canada
state: New Brunswick
city: Sault Ste Marie
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Cakovec
country: Croatia
city: Dubrovnik
country: Croatia
city: Pula
country: Croatia
city: Zagreb
country: Croatia
city: Besancon
country: France
city: Caen
country: France
city: Grenoble
country: France
city: Limoges
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Poitiers
country: France
city: Saint Herblain
country: France
city: Suresnes
country: France
city: Vandoeuvre-les-nancy
country: France
city: Bad Berka
country: Germany
city: Berlin
country: Germany
city: Grosshansdorf
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Karlsruhe
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Oldenburg
country: Germany
city: Regensburg
country: Germany
city: Ulm
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Pokfulam
country: Hong Kong
city: Shatin
country: Hong Kong
city: Edeleny
country: Hungary
city: Miskolc
country: Hungary
city: Szombathely
country: Hungary
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Kfar-Saba
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Rehovot
country: Israel
city: Aviano
country: Italy
state: Friuli-Venezia Giulia
city: Genova
country: Italy
state: Liguria
city: Milan
country: Italy
state: Lombardia
city: Monza
country: Italy
state: Lombardia
city: Rozzano
country: Italy
state: Lombardia
city: Ancona
country: Italy
state: Marche
city: Orbassano
country: Italy
state: Piemonte
city: Lido Di Camaiore
country: Italy
state: Toscana
city: Perugia
country: Italy
state: Umbria
city: Aichi
country: Japan
city: Chiba
country: Japan
city: Ehime
country: Japan
city: Fukuoka
country: Japan
city: Fukuoka
country: Japan
city: Hyogo
country: Japan
city: Hyogo
country: Japan
city: Kanagawa
country: Japan
city: Kyoto
country: Japan
city: Miyagi
country: Japan
city: Miyagi
country: Japan
city: Okayama
country: Japan
city: Okayama
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Saitama
country: Japan
city: Shizuoka
country: Japan
city: Tokyo
country: Japan
city: Tokyo
country: Japan
city: Tokyo
country: Japan
city: Tokyo
country: Japan
city: Tokyo
country: Japan
city: Yamaguchi
country: Japan
city: Gyeonggi-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Groningen
country: Netherlands
city: Maastricht
country: Netherlands
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Olsztyn
country: Poland
city: Poznan
country: Poland
city: Ivanovo
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Omsk
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Belgrade
country: Serbia
city: Belgrade
country: Serbia
city: Kragujevac
country: Serbia
city: Bloemfontein
country: South Africa
city: Johannesburg
country: South Africa
city: Sandton
country: South Africa
city: Sabadell
country: Spain
state: Barcelona
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Changhua
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taipei
country: Taiwan
city: Cherkassy
country: Ukraine
city: Chernivtsi
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Sumy
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Belfast
country: United Kingdom
city: Grimsby
country: United Kingdom
city: Leicester
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Ivor Caro, M.D.
role: STUDY_DIRECTOR
References:
citation: Koeppen H, Yu W, Zha J, Pandita A, Penuel E, Rangell L, Raja R, Mohan S, Patel R, Desai R, Fu L, Do A, Parab V, Xia X, Januario T, Louie SG, Filvaroff E, Shames DS, Wistuba I, Lipkind M, Huang J, Lazarov M, Ramakrishnan V, Amler L, Phan SC, Patel P, Peterson A, Yauch RL. Biomarker analyses from a placebo-controlled phase II study evaluating erlotinib+/-onartuzumab in advanced non-small cell lung cancer: MET expression levels are predictive of patient benefit. Clin Cancer Res. 2014 Sep 1;20(17):4488-98. doi: 10.1158/1078-0432.CCR-13-1836. Epub 2014 Mar 31.