A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab (Avastin) Plus Platinum And Paclitaxel or With Pemetrexed Plus Platinum in Patients With Non-Squamous Non-Small Cell Lung Cancer

NCT01496742 | Completed Phase 2

• 2 other identifiers: GO278212011-003719-42
• Study Type: interventional
• Target: 259
• Locations: 13 countries
• Sites: 87

Brief Summary

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RO5490258 (MetMab) in combination with either of two backbone chemotherapy regimens in the first-line setting in patients with incurable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, patients will be randomized to receive 4 cycles of bevacizumab (Avastin) 15 mg/kg iv, paclitaxel 200 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMab 15 mg/kg iv or placebo on Day 1 of each 21-day cycle. In Cohort 2, patients will be randomized to receive pemetrexed 500 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or placebo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (tumor assessments according to RECIST criteria)

  up to approximately 23 months

• Progression-free survival: Subgroup of patients with Met diagnostic positive tumors

  up to approximately 23 months

Secondary Outcomes (8)

• Overall survival

  up to approximately 23 months

• Overall response rate (tumor assessments according to RECIST criteria)

  up to approximately 23 months

• Duration of response (time from first documented objective response to disease progression)

  up to approximately 23 months

• Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)

  up to approximately 23 months

• Safety: Incidence of adverse events

  up to approximately 23 months

Study Arms (4)

Bevacizumab+MetMAb

EXPERIMENTAL

Drug: RO5490258; Drug: bevacizumab [Avastin]; Drug: cisplatin/carboplatin; Drug: paclitaxel

Bevacizumab+Placebo

ACTIVE COMPARATOR

Drug: Placebo; Drug: bevacizumab [Avastin]; Drug: cisplatin/carboplatin; Drug: paclitaxel

Pemetrexed+MetMAb

EXPERIMENTAL

Drug: RO5490258; Drug: cisplatin/carboplatin; Drug: pemetrexed

Pemetrexed+Placebo

ACTIVE COMPARATOR

Drug: Placebo; Drug: cisplatin/carboplatin; Drug: pemetrexed

Interventions

Placebo DRUG

Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle

Bevacizumab+Placebo; Pemetrexed+Placebo

RO5490258 DRUG

15 mg/kg iv, Day 1 of each 21-day cycle

Also known as: MetMAb

Bevacizumab+MetMAb; Pemetrexed+MetMAb

bevacizumab [Avastin] DRUG

15 mg/kg iv, Day 1 of each 21-day cycle

Bevacizumab+MetMAb; Bevacizumab+Placebo

cisplatin/carboplatin DRUG

standard dose iv, Day 1 of each 21-day cycle, 4 cycles

Bevacizumab+MetMAb; Bevacizumab+Placebo; Pemetrexed+MetMAb; Pemetrexed+Placebo

paclitaxel DRUG

200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles

Bevacizumab+MetMAb; Bevacizumab+Placebo

pemetrexed DRUG

500 mg/m2, Day 1 of each 21-day cycle

Pemetrexed+MetMAb; Pemetrexed+Placebo

Eligibility Criteria

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

You may qualify if:

• Adult patients, \>/= 18 years of age
• Histologically or cytologically confirmed Stage IIIB or Stage IV non-squamous non-small cell lung cancer (NSCLC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• For patients who received prior adjuvant chemotherapy or chemoradiotherapy: a treatment-free interval of at least 12 months since last chemotherapy or chemoradiotherapy cycle
• Adequate tissue for central immunohistochemical (IHC) assay of Met receptor, and epidermal growth factor receptor (EGFR) testing if EGFR status is unknown
• Radiographic evidence of disease

You may not qualify if:

• Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC
• Evidence of mixed NSCLC with a predominance of the squamous cell type
• Prior exposure to experimental treatment targeting either the hepatocyte growth factor (HGF) or Met pathway
• Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator, unless that treatment is unavailable or refused by the patient
• Known central nervous system (CNS) disease, other than stable, treated brain metastases
• History of another malignancy in the previous 3 years, except for history of in situ cancer that was treated surgically with curative intent, localized prostate cancer that has been treated surgically with curative intent, or basal or squamous cell skin cancer
• Uncontrolled diabetes
• Pregnant or lactating women
• Impaired bone marrow, liver or renal function (as defined by protocol)
• Significant history of cardiovascular disease
• Positive for HIV infection

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (87)

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Huntsville, Alabama, 35805, United States

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Scottsdale, Arizona, 85259, United States

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Bakersfield, California, 93309, United States

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Fullerton, California, 92835, United States

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Los Angeles, California, 90024, United States

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Los Angeles, California, 90095-1772, United States

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Northridge, California, 91328, United States

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San Luis Obispo, California, 93454, United States

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Santa Barbara, California, 93105, United States

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Stanford, California, 94305-5820, United States

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Grand Junction, Colorado, 81502-1628, United States

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Boynton Beach, Florida, 33435, United States

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Hollywood, Florida, 33021, United States

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Orlando, Florida, 32804, United States

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Lawrenceville, Georgia, 30045, United States

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Marietta, Georgia, 30060, United States

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Harvey, Illinois, 60426, United States

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Fort Wayne, Indiana, 46815, United States

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Fort Wayne, Indiana, 46845, United States

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Indianapolis, Indiana, 46260, United States

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Muncie, Indiana, 47303, United States

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Metairie, Louisiana, 70006, United States

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Minneapolis, Minnesota, 55454, United States

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Las Vegas, Nevada, 89148, United States

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New York, New York, 10016, United States

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Hickory, North Carolina, 28602, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43215, United States

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Middletown, Ohio, 45042, United States

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Bend, Oregon, 97701, United States

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Portland, Oregon, 97239, United States

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Seattle, Washington, 98195, United States

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Buenos Aires, C1426ANZ, Argentina

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La Rioja, F5300COE, Argentina

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Santa Rosa, L6304BOC, Argentina

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Grenoble, 38043, France

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Paris, 75230, France

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Paris, 75674, France

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Rennes, 35033, France

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Göttingen, 37075, Germany

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Halle, 06120, Germany

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Immenhausen, 34376, Germany

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München, 81925, Germany

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Münster, 48149, Germany

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Afula, 18101, Israel

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Ashkelon, 78278, Israel

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Holon, 58100, Israel

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Tel Aviv, 6423906, Israel

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Ẕerifin, 6093000, Israel

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Avellino, Campania, 83100, Italy

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Udine, Friuli Venezia Giulia, 33100, Italy

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Rome, Lazio, 00149, Italy

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Cremona, Lombardy, 26100, Italy

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Milan, Lombardy, 20133, Italy

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Orbassano, Piedmont, 10043, Italy

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Daugavpils, 5417, Latvia

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Liepāja, LV 3401, Latvia

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Riga, LV 1079, Latvia

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Riga, LV-1002, Latvia

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George Town, 10050, Malaysia

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Kuala Lumpur, 56000, Malaysia

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Negeri Sembilan, 71800, Malaysia

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Pulau Pinang, 11600, Malaysia

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Tanjung Bungah, 11200, Malaysia

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Aguascalientes, 20234, Mexico

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Chihuahua City, 31000, Mexico

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León, 37150, Mexico

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Cebu City, 6000, Philippines

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Davao City, 8000, Philippines

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Pasig, 1605, Philippines

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Quezon City, 1104, Philippines

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Quezon City, 1114, Philippines

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Barcelona, Barcelona, 08036, Spain

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Madrid, Madrid, 28007, Spain

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Madrid, Madrid, 28050, Spain

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Pamplona, Navarre, 31008, Spain

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Zaragoza, Zaragoza, 50009, Spain

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Kaohsiung City, 807, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 704, Taiwan

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Taipei, 00112, Taiwan

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Taipei, 100, Taiwan

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Aberdeen, AB25 2ZN, United Kingdom

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Birmingham, B9 5SS, United Kingdom

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Bournemouth, BH7 7DW, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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Manchester, M23 9QZ, United Kingdom

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MeSH Terms

Interventions

onartuzumab; Bevacizumab; Cisplatin; Carboplatin; Paclitaxel; Pemetrexed

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

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: December 19, 2011
• First Posted: December 21, 2011
• Study Start: April 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: September 23, 2016

Record last verified: 2016-09

Locations

IL (5); PH (5); ES (5); TW (5); IT (6); DE (5); ME (3); GB (5); FR (4); MY (5); LA (4); US (32); AR (3)