NCT01456325

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.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
494

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2012

Typical duration for phase_3

Geographic Reach
27 countries

213 active sites

Status
completed

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

First Submitted

Initial submission to the registry

October 18, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 20, 2011

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2012

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

November 2, 2016

Status Verified

November 1, 2016

Enrollment Period

4 years

First QC Date

October 18, 2011

Last Update Submit

November 1, 2016

Conditions

Outcome Measures

Primary Outcomes (1)

  • Overall Survival

    Randomization until death (up to approximately 18 months) (assessed at the treating physician's discretion using the local standard-of-care practice)

Secondary Outcomes (5)

  • European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) Scores

    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)

  • Onartuzumab Serum Concentrations

    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)

  • Percentage of Participants With Disease Progression or Death

    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)

  • Progression Free Survival (PFS)

    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)

  • Percentage of Participants with an Objective Response Assessed Using RECIST V 1.1

    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)

Study Arms (2)

Onartuzumab+Erlotinib

EXPERIMENTAL

Participants will receive onartuzumab 15 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 of every cycle of 3 weeks along with erlotinib 150 mg tablet orally once daily (QD) from Day 1, Cycle 1 until there is evidence of disease progression, death, or unacceptable toxicity, whichever occurred first.

Drug: ErlotinibDrug: Onartuzumab (MetMab)

Placebo+Erlotinib

PLACEBO COMPARATOR

Participants will receive onartuzumab matching placebo on Day 1 of every cycle of 3 weeks along with erlotinib 150 mg tablet orally QD from Day 1, Cycle 1 until there is evidence of disease progression, death, or unacceptable toxicity, whichever occurred first.

Drug: ErlotinibDrug: Placebo

Interventions

Participants will receive erlotinib 150 mg tablet orally once daily from Day 1, Cycle 1.

Also known as: Tarceva
Onartuzumab+ErlotinibPlacebo+Erlotinib

Participants will receive onartuzumab 15 mg/kg IV infusion on Day 1 of every 3-week cycle.

Also known as: RO5490258
Onartuzumab+Erlotinib

Participants will receive onartuzumab matching placebo on Day 1 of every 3-week cycle.

Placebo+Erlotinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (213)

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Chandler, Arizona, 85224, United States

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Hayward, California, 94545, United States

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Modesto, California, 95355, United States

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Oakland, California, 94611, United States

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Orange, California, 92868, United States

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Roseville, California, 95661, United States

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Sacramento, California, 95817, United States

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Sacramento, California, 95825, United States

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San Diego, California, 92108, United States

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San Francisco, California, 94115, United States

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San Jose, California, 95119, United States

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Santa Clara, California, 95051, United States

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South San Francisco, California, 94080, United States

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Vallejo, California, 94589, United States

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Walnut Creek, California, 94596, United States

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Boca Raton, Florida, 33486, United States

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Clearwater, Florida, 33761, United States

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Fort Myers, Florida, 33901, United States

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Jacksonville, Florida, 32207, United States

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Jacksonville, Florida, 32256, United States

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Chicago, Illinois, 60637, United States

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Urbana, Illinois, 61801, United States

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Bettendorf, Iowa, 52722, United States

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Sioux City, Iowa, 51101, United States

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Louisville, Kentucky, 40207, United States

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Annapolis, Maryland, 21401, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21231, United States

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Baltimore, Maryland, 21237, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Springfield, Massachusetts, 01107, United States

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Ann Arbor, Michigan, 48106, United States

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Duluth, Minnesota, 55805, United States

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St Louis, Missouri, 63110, United States

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Omaha, Nebraska, 68114, United States

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Reno, Nevada, 89502, United States

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Farmington, New Mexico, 87401, United States

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Syracuse, New York, 13210, United States

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Chapel Hill, North Carolina, 27514, United States

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Canton, Ohio, 44718, United States

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Cleveland, Ohio, 44106, United States

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Columbus, Ohio, 43210, United States

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Columbus, Ohio, 43219, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Charleston, South Carolina, 29403, United States

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Columbia, South Carolina, 29210, United States

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Chattanooga, Tennessee, 37404, United States

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Knoxville, Tennessee, 37909, United States

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Nashville, Tennessee, 37203, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77030, United States

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Bristol, Virginia, 24201, United States

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Roanoke, Virginia, 24014, United States

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La Plata, B1900BAJ, Argentina

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Quilmes, 1878, Argentina

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Santa Fe, S3000FFU, Argentina

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Camperdown, New South Wales, 2050, Australia

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Waratah, New South Wales, 2298, Australia

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Chermside, Queensland, 4032, Australia

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Adelaide, South Australia, 5041, Australia

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Parkville, Victoria, 3050, Australia

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Gilly (Charleroi), 6000, Belgium

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Liège, 4000, Belgium

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Namur, 5000, Belgium

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Salvador/BA, Estado de Bahia, 41820-021, Brazil

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Lajeado, Rio Grande do Sul, 95900-000, Brazil

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Novo Hamburgo, Rio Grande do Sul, 93510-250, Brazil

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Jaú, São Paulo, 17210-080, Brazil

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São Paulo, São Paulo, 08270-070, Brazil

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Sorocaba, São Paulo, 18030-005, Brazil

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Saint John, New Brunswick, E2L 4L2, Canada

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Sault Ste. Marie, Ontario, P6A 2C4, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Montreal, Quebec, J4B 5Z7, Canada

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Santiago, 0, Chile

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Santiago, Providencia, Chile

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Temuco, 4810469, Chile

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Čakovec, 40000, Croatia

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Dubrovnik, 20000, Croatia

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Pula, 52100, Croatia

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Zagreb, 10000, Croatia

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Besançon, 25030, France

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Caen, 14076, France

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Grenoble, 38 043, France

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Limoges, 87042, France

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Marseille, 13915, France

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Montpellier, 34295, France

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Paris, 75970, France

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Poitiers, 86021, France

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Saint-Herblain, 44805, France

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Suresnes, 92151, France

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Vandœuvre-lès-Nancy, 54511, France

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Bad Berka, 99437, Germany

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Berlin, 14165, Germany

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Großhansdorf, 22927, Germany

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Hamburg, 21075, Germany

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Heidelberg, 69126, Germany

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Karlsruhe, 76137, Germany

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Mainz, 55131, Germany

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München, 80336, Germany

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Oldenburg, 26121, Germany

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Regensburg, 93053, Germany

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Ulm, 89081, Germany

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Villingen-Schwenningen, 78052, Germany

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Pokfulam, Hong Kong

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Shatin, Hong Kong

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Edelény, 3780, Hungary

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Miskolc, 3529, Hungary

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Szombathely, 9700, Hungary

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Cork, Ireland

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Dublin, 8, Ireland

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Beersheba, 8410101, Israel

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Haifa, 4959381, Israel

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Jerusalem, 91120-01, Israel

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Jerusalem, 9372212, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5262100, Israel

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Rehovot, 76100, Israel

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Aviano, Friuli Venezia Giulia, 33081, Italy

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Genoa, Liguria, 16132, Italy

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Milan, Lombardy, 20141, Italy

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Monza, Lombardy, 20900, Italy

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Rozzano, Lombardy, 20089, Italy

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Orbassano, Piedmont, 10043, Italy

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Ancona, The Marches, 60121, Italy

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Lido di Camaiore, Tuscany, 55043, Italy

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Perugia, Umbria, 06123, Italy

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Aichi, 464-8681, Japan

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Chiba, 277-8577, Japan

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Ehime, 791-0280, Japan

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Fukuoka, 811-1395, Japan

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Fukuoka, 812-8582, Japan

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Hyōgo, 650-0047, Japan

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Hyōgo, 673-8553, Japan

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Kanagawa, 236-0051, Japan

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Kyoto, 606-8507, Japan

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Miyagi, 980-8574, Japan

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Miyagi, 981-1293, Japan

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Okayama, 700-8558, Japan

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Okayama, 710-8602, Japan

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Osaka, 534-0021, Japan

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Osaka, 537-8511, Japan

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Osaka, 589-8511, Japan

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Osaka, 591-8555, Japan

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Saitama, 362-0806, Japan

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Shizuoka, 411-8777, Japan

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Tokyo, 104-0045, Japan

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Tokyo, 113-8677, Japan

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Tokyo, 135-8550, Japan

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Tokyo, 160-0023, Japan

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Tokyo, 173-8605, Japan

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Yamaguchi, 755-0241, Japan

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Amsterdam, 1081 HV, Netherlands

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Groningen, 9700 RB, Netherlands

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Maastricht, 6229 HX, Netherlands

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Lima, L27, Peru

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Lima, Lima 1, Peru

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Lima, Lima 27, Peru

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Gdansk, 80-952, Poland

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Krakow, 31-531, Poland

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Lodz, 93-509, Poland

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Olsztyn, 10-357, Poland

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Poznan, Poland

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Ivanovo, 153040, Russia

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Krasnodar, 350040, Russia

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Omsk, 644013, Russia

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Saint Petersburg, 189646, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197101, Russia

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Tomsk, 634050, Russia

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Belgrade, 11000, Serbia

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Belgrade, 11080, Serbia

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Kragujevac, 34000, Serbia

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Bloemfontein, 9301, South Africa

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Johannesburg, 2193, South Africa

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Sandton, 2196, South Africa

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Gyeonggi-do, 443-380, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Seoul, 120-752, South Korea

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08036, Spain

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Barcelona, Barcelona, 08041, Spain

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Barcelona, Barcelona, 08916, Spain

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Sabadell, Barcelona, 08208, Spain

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Madrid, Madrid, 28007, Spain

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Madrid, Madrid, 28034, Spain

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Madrid, Madrid, 28050, Spain

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Madrid, Madrid, 28222, Spain

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Seville, Sevilla, 41013, Spain

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Valencia, Valencia, 41014, Spain

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Changhua, 500, Taiwan

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Kaohsiung City, 813, Taiwan

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Taipei, 100, Taiwan

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Cherkassy, 18009, Ukraine

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Chernivtsi, 58013, Ukraine

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Dnipropetrovsk, 49102, Ukraine

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Sumy, 40005, Ukraine

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Zaporizhzhya, 69040, Ukraine

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Belfast, BT9 7AB, United Kingdom

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Grimsby, DN33 2BA, United Kingdom

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Leicester, LE1 5WW, United Kingdom

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London, SE1 9RT, United Kingdom

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London, SW10 9NH, United Kingdom

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Manchester, M2O 4BX, United Kingdom

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Related Publications (1)

  • 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.

MeSH Terms

Interventions

Erlotinib Hydrochlorideonartuzumab

Intervention Hierarchy (Ancestors)

QuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Ivor Caro, M.D.

    Genentech, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 18, 2011

First Posted

October 20, 2011

Study Start

January 1, 2012

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

November 2, 2016

Record last verified: 2016-11

Locations