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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01496742
First received: December 19, 2011
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

This multicenter, randomized, double-blind, placebo-controlled study will evalua te the efficacy and safety of RO5490258 (MetMab) in combination with either of t wo backbone chemotherapy regimens in the first-line setting in patients with inc urable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, pa tients 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 Met Mab 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/carbo platin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cyc le. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or place bo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). Anticipate d time on study treatment is until disease progression or unacceptable toxicity occurs.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: RO5490258
Drug: bevacizumab [Avastin]
Drug: pemetrexed
Drug: Placebo
Drug: cisplatin/carboplatin
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Progression-free survival (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Progression-free survival: Subgroup of patients with Met diagnostic positive tumors [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Overall response rate (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Duration of response (time from first documented objective response to disease progression) [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: up to approximately 23 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: serum concentration (Cmin/Cmax) [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Serum levels of anti-therapeutic antibodies (MetMAb ATAs) [ Time Frame: Pre-dose Day 1 of Cycles 1, 2 and 4 ] [ Designated as safety issue: No ]

Enrollment: 258
Study Start Date: April 2012
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab+MetMAb Drug: RO5490258
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: bevacizumab [Avastin]
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Drug: paclitaxel
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
Active Comparator: Bevacizumab+Placebo Drug: bevacizumab [Avastin]
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: Placebo
Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Drug: paclitaxel
200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
Experimental: Pemetrexed+MetMAb Drug: RO5490258
15 mg/kg iv, Day 1 of each 21-day cycle
Drug: pemetrexed
500 mg/m2, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles
Active Comparator: Pemetrexed+Placebo Drug: pemetrexed
500 mg/m2, Day 1 of each 21-day cycle
Drug: Placebo
Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
Drug: cisplatin/carboplatin
standard dose iv, Day 1 of each 21-day cycle, 4 cycles

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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: a treatment-free interval of at least 12 months since last chemotherapy cycle
  • Adequate tissue for central IHC assay of Met receptor, and 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 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
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01496742

  Hide Study Locations
Locations
United States, Alabama
Huntsville, Alabama, United States, 35805
United States, Arizona
Scottsdale, Arizona, United States, 85259
United States, California
Bakersfield, California, United States, 93309
Fullerton, California, United States, 92835
Los Angeles, California, United States, 90095-1772
Los Angeles, California, United States, 90024
Northridge, California, United States, 91325
San Luis Obispo, California, United States, 93454
Santa Barbara, California, United States, 93105
Stanford, California, United States, 94305-5820
United States, Colorado
Grand Junction, Colorado, United States, 81502-1628
United States, Florida
Boynton Beach, Florida, United States, 33435
Hollywood, Florida, United States, 33021
Orlando, Florida, United States, 32804
United States, Georgia
Lawrenceville, Georgia, United States, 30045
Marietta, Georgia, United States, 30060
United States, Illinois
Harvey, Illinois, United States, 60426
United States, Indiana
Fort Wayne, Indiana, United States, 46815
Fort Wayne, Indiana, United States, 46845
Indianapolis, Indiana, United States, 46260
Muncie, Indiana, United States, 47303
United States, Louisiana
Metairie, Louisiana, United States, 70006
United States, Minnesota
Minneapolis, Minnesota, United States, 55454
United States, Nevada
Las Vegas, Nevada, United States, 89148
United States, New York
New York, New York, United States, 10016
United States, North Carolina
Hickory, North Carolina, United States, 28602
United States, Ohio
Cleveland, Ohio, United States, 44195
Columbus, Ohio, United States, 43215
Middletown, Ohio, United States, 45042
United States, Oregon
Bend, Oregon, United States, 97701
Portland, Oregon, United States, 97239
United States, Washington
Seattle, Washington, United States, 98195
Argentina
Buenos Aires, Argentina, C1426ANZ
La Rioja, Argentina, F5300COE
Santa Rosa, Argentina, L6304BOC
France
Grenoble, France, 38043
Paris, France, 75674
Paris, France, 75230
Rennes, France, 35033
Germany
Göttingen, Germany, 37075
Halle (Saale), Germany, 06120
Immenhausen, Germany, 34376
München, Germany, 81925
Münster, Germany, 48149
Israel
Afula, Israel, 18101
Ashkelon, Israel, 78278
Holon, Israel, 58100
Tel Aviv, Israel, 6423906
Zerifin, Israel, 6093000
Italy
Avellino, Campania, Italy, 83100
Udine, Friuli-Venezia Giulia, Italy, 33100
Roma, Lazio, Italy, 00149
Cremona, Lombardia, Italy, 26100
Milano, Lombardia, Italy, 20133
Orbassano, Piemonte, Italy, 10043
Latvia
Daugavpils, Latvia, 5417
Liepaja, Latvia, LV 3401
Riga, Latvia, LV-1002
Riga, Latvia, LV 1079
Malaysia
Kuala Lumpur, Malaysia, 56000
Negeri Sembilan, Malaysia, 71800
Penang, Malaysia, 10050
Pulau Pinang, Malaysia, 11600
Tanjung Bungah, Malaysia, 11200
Mexico
Aguascalientes, Mexico, 20234
Chihuahua, Mexico, 31000
Leon, Mexico, 37150
Philippines
CEBU City, Philippines, 6000
Davao City, Philippines, 8000
Pasig City, Philippines, 1605
Quezon City, Philippines, 1114
Quezon City, Philippines, 1104
Spain
Pamplona, Navarra, Spain, 31008
Barcelona, Spain, 08036
Madrid, Spain, 28007
Madrid, Spain, 28050
Zaragoza, Spain, 50009
Taiwan
Kaohsiung, Taiwan, 807
Taichung, Taiwan, 40705
Tainan, Taiwan, 704
Taipei, Taiwan, 00112
Taipei, Taiwan, 100
United Kingdom
Aberdeen, United Kingdom, AB25 2ZN
Birmingham, United Kingdom, B9 5SS
Bournemouth, United Kingdom, BH7 7DW
Leeds, United Kingdom, LS9 7TF
Manchester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01496742     History of Changes
Other Study ID Numbers: GO27821, 2011-003719-42
Study First Received: December 19, 2011
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Bevacizumab
Pemetrexed
Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 18, 2014