Clinical trial NCT01496742: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Squamous Non-Small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-21
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-free survival (tumor assessments according to RECIST criteria)
timeFrame: up to approximately 23 months
measure: Progression-free survival: Subgroup of patients with Met diagnostic positive tumors
timeFrame: up to approximately 23 months
Secondary outcomes:
measure: Overall survival
timeFrame: up to approximately 23 months
measure: Overall response rate (tumor assessments according to RECIST criteria)
timeFrame: up to approximately 23 months
measure: Duration of response (time from first documented objective response to disease progression)
timeFrame: up to approximately 23 months
measure: Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)
timeFrame: up to approximately 23 months
measure: Safety: Incidence of adverse events
timeFrame: up to approximately 23 months
measure: Pharmacokinetics: serum concentration (Cmin/Cmax)
timeFrame: Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination
measure: Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb
timeFrame: Pre- and post-dose on Day 1 of Cycles 1 and 4
measure: Serum levels of anti-therapeutic antibodies (MetMAb ATAs)
timeFrame: Pre-dose Day 1 of Cycles 1, 2 and 4
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Bakersfield
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Northridge
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Stanford
country: United States
state: California
city: Grand Junction
country: United States
state: Colorado
city: Boynton Beach
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Lawrenceville
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Harvey
country: United States
state: Illinois
city: Fort Wayne
country: United States
state: Indiana
city: Fort Wayne
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Muncie
country: United States
state: Indiana
city: Metairie
country: United States
state: Louisiana
city: Minneapolis
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: New York
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Middletown
country: United States
state: Ohio
city: Bend
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: La Rioja
country: Argentina
city: Santa Rosa
country: Argentina
city: Grenoble
country: France
city: Paris
country: France
city: Paris
country: France
city: Rennes
country: France
city: Göttingen
country: Germany
city: Halle (Saale)
country: Germany
city: Immenhausen
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Holon
country: Israel
city: Tel Aviv
country: Israel
city: Zerifin
country: Israel
city: Avellino
country: Italy
state: Campania
city: Udine
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Cremona
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Orbassano
country: Italy
state: Piemonte
city: Daugavpils
country: Latvia
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Kuala Lumpur
country: Malaysia
city: Negeri Sembilan
country: Malaysia
city: Penang
country: Malaysia
city: Pulau Pinang
country: Malaysia
city: Tanjung Bungah
country: Malaysia
city: Aguascalientes
country: Mexico
city: Chihuahua
country: Mexico
city: Leon
country: Mexico
city: CEBU City
country: Philippines
city: Davao City
country: Philippines
city: Pasig City
country: Philippines
city: Quezon City
country: Philippines
city: Quezon City
country: Philippines
city: Pamplona
country: Spain
state: Navarra
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Zaragoza
country: Spain
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Aberdeen
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Bournemouth
country: United Kingdom
city: Leeds
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: