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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

Primary Purpose

Non-Squamous Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
RO5490258
bevacizumab [Avastin]
cisplatin/carboplatin
paclitaxel
pemetrexed
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Squamous Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Bevacizumab+MetMAb

Bevacizumab+Placebo

Pemetrexed+MetMAb

Pemetrexed+Placebo

Arm Description

Outcomes

Primary Outcome Measures

Progression-free survival (tumor assessments according to RECIST criteria)
Progression-free survival: Subgroup of patients with Met diagnostic positive tumors

Secondary Outcome Measures

Overall survival
Overall response rate (tumor assessments according to RECIST criteria)
Duration of response (time from first documented objective response to disease progression)
Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)
Safety: Incidence of adverse events
Pharmacokinetics: serum concentration (Cmin/Cmax)
Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb
Serum levels of anti-therapeutic antibodies (MetMAb ATAs)

Full Information

First Posted
December 19, 2011
Last Updated
September 21, 2016
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01496742
Brief Title
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
Official Title
A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Metmab Vs. Placebo in Combination With Either Bevacizumab + Platinum + Paclitaxel or Pemetrexed + Platinum in Patients With Untreated Stage IIIb or IV Non-Squamous NSCLC
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Squamous Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
259 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab+MetMAb
Arm Type
Experimental
Arm Title
Bevacizumab+Placebo
Arm Type
Active Comparator
Arm Title
Pemetrexed+MetMAb
Arm Type
Experimental
Arm Title
Pemetrexed+Placebo
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
RO5490258
Other Intervention Name(s)
MetMAb
Intervention Description
15 mg/kg iv, Day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
15 mg/kg iv, Day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
cisplatin/carboplatin
Intervention Description
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
Intervention Type
Drug
Intervention Name(s)
pemetrexed
Intervention Description
500 mg/m2, Day 1 of each 21-day cycle
Primary Outcome Measure Information:
Title
Progression-free survival (tumor assessments according to RECIST criteria)
Time Frame
up to approximately 23 months
Title
Progression-free survival: Subgroup of patients with Met diagnostic positive tumors
Time Frame
up to approximately 23 months
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
up to approximately 23 months
Title
Overall response rate (tumor assessments according to RECIST criteria)
Time Frame
up to approximately 23 months
Title
Duration of response (time from first documented objective response to disease progression)
Time Frame
up to approximately 23 months
Title
Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)
Time Frame
up to approximately 23 months
Title
Safety: Incidence of adverse events
Time Frame
up to approximately 23 months
Title
Pharmacokinetics: serum concentration (Cmin/Cmax)
Time Frame
Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination
Title
Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb
Time Frame
Pre- and post-dose on Day 1 of Cycles 1 and 4
Title
Serum levels of anti-therapeutic antibodies (MetMAb ATAs)
Time Frame
Pre-dose Day 1 of Cycles 1, 2 and 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1772
Country
United States
City
Northridge
State/Province
California
ZIP/Postal Code
91328
Country
United States
City
San Luis Obispo
State/Province
California
ZIP/Postal Code
93454
Country
United States
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5820
Country
United States
City
Grand Junction
State/Province
Colorado
ZIP/Postal Code
81502-1628
Country
United States
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33435
Country
United States
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30045
Country
United States
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
City
Harvey
State/Province
Illinois
ZIP/Postal Code
60426
Country
United States
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47303
Country
United States
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28602
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
City
Middletown
State/Province
Ohio
ZIP/Postal Code
45042
Country
United States
City
Bend
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Buenos Aires
ZIP/Postal Code
C1426ANZ
Country
Argentina
City
La Rioja
ZIP/Postal Code
F5300COE
Country
Argentina
City
Santa Rosa
ZIP/Postal Code
L6304BOC
Country
Argentina
City
Grenoble
ZIP/Postal Code
38043
Country
France
City
Paris
ZIP/Postal Code
75230
Country
France
City
Paris
ZIP/Postal Code
75674
Country
France
City
Rennes
ZIP/Postal Code
35033
Country
France
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
City
Halle (Saale)
ZIP/Postal Code
06120
Country
Germany
City
Immenhausen
ZIP/Postal Code
34376
Country
Germany
City
München
ZIP/Postal Code
81925
Country
Germany
City
Münster
ZIP/Postal Code
48149
Country
Germany
City
Afula
ZIP/Postal Code
18101
Country
Israel
City
Ashkelon
ZIP/Postal Code
78278
Country
Israel
City
Holon
ZIP/Postal Code
58100
Country
Israel
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
City
Zerifin
ZIP/Postal Code
6093000
Country
Israel
City
Avellino
State/Province
Campania
ZIP/Postal Code
83100
Country
Italy
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
00149
Country
Italy
City
Cremona
State/Province
Lombardia
ZIP/Postal Code
26100
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Orbassano
State/Province
Piemonte
ZIP/Postal Code
10043
Country
Italy
City
Daugavpils
ZIP/Postal Code
5417
Country
Latvia
City
Liepaja
ZIP/Postal Code
LV 3401
Country
Latvia
City
Riga
ZIP/Postal Code
LV 1079
Country
Latvia
City
Riga
ZIP/Postal Code
LV-1002
Country
Latvia
City
Kuala Lumpur
ZIP/Postal Code
56000
Country
Malaysia
City
Negeri Sembilan
ZIP/Postal Code
71800
Country
Malaysia
City
Penang
ZIP/Postal Code
10050
Country
Malaysia
City
Pulau Pinang
ZIP/Postal Code
11600
Country
Malaysia
City
Tanjung Bungah
ZIP/Postal Code
11200
Country
Malaysia
City
Aguascalientes
ZIP/Postal Code
20234
Country
Mexico
City
Chihuahua
ZIP/Postal Code
31000
Country
Mexico
City
Leon
ZIP/Postal Code
37150
Country
Mexico
City
CEBU City
ZIP/Postal Code
6000
Country
Philippines
City
Davao City
ZIP/Postal Code
8000
Country
Philippines
City
Pasig City
ZIP/Postal Code
1605
Country
Philippines
City
Quezon City
ZIP/Postal Code
1104
Country
Philippines
City
Quezon City
ZIP/Postal Code
1114
Country
Philippines
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28050
Country
Spain
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
City
Taipei
ZIP/Postal Code
00112
Country
Taiwan
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M23 9QZ
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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