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 - Full Text View

Purpose

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.

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:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Paclitaxel Carboplatin Pemetrexed Pemetrexed disodium Bevacizumab

U.S. FDA Resources

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 ]

Estimated Enrollment:	260
Study Start Date:	April 2012
Estimated Study Completion Date:	May 2014
Estimated Primary Completion Date:	December 2013 (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 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
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 Other Name: MetMAb 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

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

Contacts

Contact: Please reference Study ID Number: GO27821 www.roche.com/about_roche/roche_worldwide.htm

888-662-6728 (U.S. Only)

genentechclinicaltrials@druginfo.com

Show 108 Study Locations

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:	December 5, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Bevacizumab
Cisplatin
Carboplatin
Paclitaxel

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013