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
- Conditions
- Non-Squamous Non-Small Cell Lung Cancer
- Interventions
- Drug: PlaceboDrug: cisplatin/carboplatin
- Registration Number
- NCT01496742
- Lead Sponsor
- Genentech, Inc.
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 259
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bevacizumab+MetMAb bevacizumab [Avastin] - Bevacizumab+MetMAb cisplatin/carboplatin - Bevacizumab+Placebo Placebo - Bevacizumab+Placebo cisplatin/carboplatin - Pemetrexed+MetMAb RO5490258 - Bevacizumab+MetMAb RO5490258 - Pemetrexed+MetMAb cisplatin/carboplatin - Pemetrexed+Placebo Placebo - Pemetrexed+Placebo cisplatin/carboplatin - Bevacizumab+Placebo bevacizumab [Avastin] - Bevacizumab+MetMAb paclitaxel - Bevacizumab+Placebo paclitaxel - Pemetrexed+MetMAb pemetrexed - Pemetrexed+Placebo pemetrexed -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Safety: Incidence of adverse events up to approximately 23 months 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 Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb Pre- and post-dose on Day 1 of Cycles 1 and 4 Pharmacokinetics: serum concentration (Cmin/Cmax) Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination Serum levels of anti-therapeutic antibodies (MetMAb ATAs) Pre-dose Day 1 of Cycles 1, 2 and 4