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

Tracking Information
First Submitted Date ICMJE	December 19, 2011
First Posted Date ICMJE	December 21, 2011
Last Update Posted Date	September 23, 2016
Study Start Date ICMJE	April 2012
Actual Primary Completion Date	November 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 19, 2011)	Progression-free survival (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 23 months ]; Progression-free survival: Subgroup of patients with Met diagnostic positive tumors [ Time Frame: up to approximately 23 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01496742 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: December 19, 2011)	Overall survival [ Time Frame: up to approximately 23 months ]; Overall response rate (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 23 months ]; Duration of response (time from first documented objective response to disease progression) [ Time Frame: up to approximately 23 months ]; 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 ]; Safety: Incidence of adverse events [ Time Frame: up to approximately 23 months ]; Pharmacokinetics: serum concentration (Cmin/Cmax) [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination ]; 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 ]; Serum levels of anti-therapeutic antibodies (MetMAb ATAs) [ Time Frame: Pre-dose Day 1 of Cycles 1, 2 and 4 ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	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 ICMJE	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
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
Condition ICMJE	Non-Squamous Non-Small Cell Lung Cancer
Intervention ICMJE	Drug: Placebo Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle; Drug: RO5490258 15 mg/kg iv, Day 1 of each 21-day cycle Other Name: MetMAb; 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; Drug: pemetrexed 500 mg/m2, Day 1 of each 21-day cycle
Study Arms	Experimental: Bevacizumab+MetMAb Interventions: Drug: RO5490258 Drug: bevacizumab [Avastin] Drug: cisplatin/carboplatin Drug: paclitaxel; Active Comparator: Bevacizumab+Placebo Interventions: Drug: Placebo Drug: bevacizumab [Avastin] Drug: cisplatin/carboplatin Drug: paclitaxel; Experimental: Pemetrexed+MetMAb Interventions: Drug: RO5490258 Drug: cisplatin/carboplatin Drug: pemetrexed; Active Comparator: Pemetrexed+Placebo Interventions: Drug: Placebo Drug: cisplatin/carboplatin Drug: pemetrexed
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: September 21, 2016)	259
Original Estimated Enrollment ICMJE; (submitted: December 19, 2011)	260
Actual Study Completion Date	November 2015
Actual Primary Completion Date	November 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, France, Germany, Israel, Italy, Latvia, Malaysia, Mexico, Philippines, Spain, Taiwan, United Kingdom, United States
Removed Location Countries	Brazil, Portugal, Russian Federation
Administrative Information
NCT Number ICMJE	NCT01496742
Other Study ID Numbers ICMJE	GO27821; 2011-003719-42 ( EudraCT Number )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Genentech, Inc.
Study Sponsor ICMJE	Genentech, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Clinical Trials Genentech, Inc.
PRS Account	Genentech, Inc.
Verification Date	September 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP